[gmx-users] PMF in inhomogeneous fluid phase

[Andreas Mecklenfeld]

Dear Gromacs-users,

I have a question that may not be directly Gromacs-related. I want to 
calculate the potential of mean force (PMF) for a solute that is pulled 
away from a crystal surface. The issue is that the fluid phase is 
inhomogeneous, as it consists of water and cluster-forming ions. From my 
understanding, this would make the PMF calculation not only dependent on 
the pull-coordinate (z-axis of the simulation box), but the PMF would be 
also influenced by the position of the clusters which might change their 
position randomly in different umbrella windows. One could restrain the 
positions of the ions to freeze the local composition. However, this 
would be an enormous interference into the system and I'm not really 
comfortable in doing so.


Any suggestions would be highly appreciated.

Bests,
Andreas

--
M. Sc. Andreas Mecklenfeld
Technische Universität Braunschweig
Institut für Thermodynamik
Hans-Sommer-Straße 5
38106 Braunschweig
Deutschland / Germany

Tel: +49 (0)531 391-2634
 +49 (0)531 391-65685
Fax: +49 (0)531 391-7814

https://www.tu-braunschweig.de/ift
https://www.tu-braunschweig.de/ift/agmolth

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[gmx-users] PMF wrong when calculating dihedral angle rotate

[yujie Liu]

Dear gmx users,
  I want to repeat a amber tutorial
*http://ambermd.org/tutorials/advanced/tutorial17/index.htm
* by using
gromacs, which is about PMF calculation of Alanine Dipeptide Phi/Psi
Rotation.
 Everything is ok about the process of simulation, firstly equilibrium and
generate a series of configuration, then do long simulation respectively.
  However, When using "gmx whan -it tpr.dat -if/x pullf/x.dat -cycl"
command  to generate PMF curve, I found histo.xvg figure is very good
but profile.xvg figure is wrong. Then I check the data of profile.xvg file,
found the second column data is "-nan". I also assign -min and -max, but
still wrong.
  Finally, I found same question on the internet, the URL is
*https://mailman-1.sys.kth.se/pipermail/gromacs.org_gmx-users/2016-August/108093.html
*
and *https://redmine.gromacs.org/issues/2609
* . At the same time, I repeat
this a sample PMF
(*https://redmine.gromacs.org/attachments/2405/gwham_error_sample.tar.gz
*)
about angle by "gmx wham", I also found "profile.xvg" is wrong.
  I use GROMACS 2019.3. I hope some expert can give me some good advice.
Whether the gromacs software can not generate correct PMF of angle?
  Thank you,
  YUjie Liu
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[gmx-users] PMF from constant force..

[Nikhil Maroli]

Dear all,

Is there any way to obtain PMF from; pull  =  constant force.? I have seen
wham only supports 'umbrella'

When i try to use umbrella my molecule is not travelling through the
channel.

Thanks in advance.
-- 
Regards,
Nikhil Maroli
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[gmx-users] PMF calculation: molecule though the channel.

[Nikhil Maroli]

Dear all,

Im trying to pull water molecules through Aquaporin channel with the
following pull parameters (to obtain PMF). On visualising the trajectory,
water molecules travelling around the surface/outside of aquaporin instead
of going through inside. How I can make sure that the water molecule is
going through the channel, I tried different values of k, pulling rate and
kept water at the top and the middle region (inside) of the channel, still
it is not travelling though the channel.

pull_ngroups= 2
pull_ncoords= 1
pull_group1_name= Chain_B
pull_group2_name= Chain_A
pull_coord1_type= umbrella
pull_coord1_geometry= direction-periodic
pull_coord1_groups  = 1 2
pull-coord1-vec = 0 0 1
pull_coord1_rate= 0.1  ; 0.01 nm per ps = 10 nm per ns
pull_coord1_k   = 100
pull_coord1_start   = yes


I would be appreciative of any suggestions



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Regards,
Nikhil Maroli
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[gmx-users] PMF ligand membrane protein

[nahren manuel]

Dear Gromacs User,
this is the first time I am attempting membrane protein simulation.
I wish to obtain a PMF value for a ligand permeating through a membrane protein 
(lacY permease). In the Xray str. the ligand is almost at the center of the 
protein. I wish to generate enough initial configurations (using N N Y, along 
'z' axis) prior to starting umbrella sampling. the ligand of course is being 
pulled, but which part should I keep as reference (or should I look for another 
alternative). I was thinking of pull_geometry = reference, but since this 
option has been left out in GMX 5.1.4, I do not know what to keep as the 
reference. Some assistance on how to proceed would be helpful. 
Thanks.
Best,nahren
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Re: [gmx-users] PMF - US histograms problem

[Sajeewa Pemasinghe]

Hi,

When I get  a region sparsely populated like that, I increase the number of
points in that particular region and increase the k value to about 3000 but
not more than that. Increasing the k value to something like 2 will
result in the distribution getting very narrow and therefore further
hindering the overlap. It could also be that the coordinate(path) you have
chosen is not a good one to pull the peptide out. Changing the
pull_geometry from distance to cylinder might also help as used in this
article.

http://www.cell.com/biophysj/fulltext/S0006-3495(12)01180-0

Best,

Sajeewa



On Mon, Mar 27, 2017 at 1:50 PM, Eudes Fileti  wrote:

> Hi everyone, I'm trying to calculate the PMF for the extraction of a
> peptide from within a peptide nanostructure. However I'm having difficulty
> to overlap the histograms for the first pulling windows: Many full overlap
> windows follow by a large gap with no histogram.
>
> I've tried the two things I could: reduce the distance increment between
> the windows (now I'm using 0.05nm), and I've already done several tests
> with different force constants with k up to 2! For each window test I
> run only 1ns of sampling.
>
> Anyone have any suggestions? Could another umbrella sampling scheme
> (constraint pulling) be more efficient in this case?
>
> Bests
> ___
> Eudes Eterno Fileti
> Instituto de Ciência e Tecnologia da UNIFESP
> Av. Cesar Lattes, 1201, Eugênio de Mello, SP, 12247-014
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[gmx-users] PMF - US histograms problem

[Eudes Fileti]

Hi everyone, I'm trying to calculate the PMF for the extraction of a
peptide from within a peptide nanostructure. However I'm having difficulty
to overlap the histograms for the first pulling windows: Many full overlap
windows follow by a large gap with no histogram.

I've tried the two things I could: reduce the distance increment between
the windows (now I'm using 0.05nm), and I've already done several tests
with different force constants with k up to 2! For each window test I
run only 1ns of sampling.

Anyone have any suggestions? Could another umbrella sampling scheme
(constraint pulling) be more efficient in this case?

Bests
___
Eudes Eterno Fileti
Instituto de Ciência e Tecnologia da UNIFESP
Av. Cesar Lattes, 1201, Eugênio de Mello, SP, 12247-014
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Re: [gmx-users] PMF, Enthalpy, Entropy

[David van der Spoel]

On 14/03/17 13:23, Justin Lemkul wrote:



On 3/13/17 2:11 PM, Alex wrote:

Hello all,

I have the calculated the PMF for the adsorption of a peptide into a
solid
surface using umbrella sampling, a 60 ns of NVT-production for each
window
was considered so that the PMF is well converged.
Now, following a nice paper by Prof. van der Spoel "*DOI:
*10.1021/ct400404q"
and in the same fashion as (Fig.4 of the paper) I also would like to
calculate the enthalpy and entropy along the reaction coordinate of
the PMF.

To do so, for each window I calculated the enthalpy via "gmx energy
case.edr ... " and selected "potential" as in the NVT ensemble, enthalpy
and potential are identical. And then using the Gibbs free energy
equationI
calculated the "- [T*\Delat S]", so that at the end I have all of three
quantity as a function of the reaction coordinate.

I do not know why the PMF and Enthalpy (potential) are not in the same(or
close) order of magnitude.  The trusted PMF is around "60 kcal/mol=251.0
kj/mol" while the Enthalpy is something like "-1557.92e+03 kj/mol", I was
wondering if the unit of enthalpy (potential) here is really meaningful?
Does the enthalpy's unit is "kj/mol" or "j/mol", as a division to "1000"
could give more sense to it?

I know the convergence of the enthalpy is hard respect to the convergence
of the PMF, but, here the convergence is not the matter, rather the
unit of
enthalpy is the matter.

Here is the potential average of enthalpy (potential) for one of the
window
via gmx energy:

Energy  Average   Err.Est.   RMSD  Tot-Drift


Potential-1.5579e+06 14726.909-14.203
(kJ/mol)

Which of the "Err,Est" or "Tot-Drift" is the error bar for enthalpy
(potential)?

And finally, what does the "normalization to zero at infinite distance"
means?



Because if you're just calculating the enthalpy of a system, that
includes (presumably) a ton of solvent-solvent interaction energy that
doesn't affect the binding free energy.  So the enthalpy of the window
in which the binding species are at the maximum distance is set to zero,
e.g. the reference of the unbound state.  Then all subsequent enthalpy
values are offset by the same amount so you have DeltaH and not just H.

If I've messed that up, maybe David will correct me; I read that paper
but it's been a while so I may be wrong on teh details.



This is correct and what we have done too. The main problem is that it 
is harder to have the enthalpy converge than the free energy, that is it 
requires more sampling.



-Justin





--
David van der Spoel, Ph.D., Professor of Biology
Dept. of Cell & Molec. Biol., Uppsala University.
Box 596, 75124 Uppsala, Sweden. Phone:  +46184714205.
sp...@xray.bmc.uu.sehttp://folding.bmc.uu.se
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Re: [gmx-users] PMF, Enthalpy, Entropy

[Justin Lemkul]

On 3/13/17 2:11 PM, Alex wrote:

Hello all,

I have the calculated the PMF for the adsorption of a peptide into a solid
surface using umbrella sampling, a 60 ns of NVT-production for each window
was considered so that the PMF is well converged.
Now, following a nice paper by Prof. van der Spoel "*DOI: *10.1021/ct400404q"
and in the same fashion as (Fig.4 of the paper) I also would like to
calculate the enthalpy and entropy along the reaction coordinate of the PMF.

To do so, for each window I calculated the enthalpy via "gmx energy
case.edr ... " and selected "potential" as in the NVT ensemble, enthalpy
and potential are identical. And then using the Gibbs free energy equationI
calculated the "- [T*\Delat S]", so that at the end I have all of three
quantity as a function of the reaction coordinate.

I do not know why the PMF and Enthalpy (potential) are not in the same(or
close) order of magnitude.  The trusted PMF is around "60 kcal/mol=251.0
kj/mol" while the Enthalpy is something like "-1557.92e+03 kj/mol", I was
wondering if the unit of enthalpy (potential) here is really meaningful?
Does the enthalpy's unit is "kj/mol" or "j/mol", as a division to "1000"
could give more sense to it?

I know the convergence of the enthalpy is hard respect to the convergence
of the PMF, but, here the convergence is not the matter, rather the unit of
enthalpy is the matter.

Here is the potential average of enthalpy (potential) for one of the window
via gmx energy:

Energy  Average   Err.Est.   RMSD  Tot-Drift

Potential-1.5579e+06 14726.909-14.203
(kJ/mol)

Which of the "Err,Est" or "Tot-Drift" is the error bar for enthalpy
(potential)?

And finally, what does the "normalization to zero at infinite distance"
means?



Because if you're just calculating the enthalpy of a system, that includes 
(presumably) a ton of solvent-solvent interaction energy that doesn't affect the 
binding free energy.  So the enthalpy of the window in which the binding species 
are at the maximum distance is set to zero, e.g. the reference of the unbound 
state.  Then all subsequent enthalpy values are offset by the same amount so you 
have DeltaH and not just H.


If I've messed that up, maybe David will correct me; I read that paper but it's 
been a while so I may be wrong on teh details.


-Justin


--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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[gmx-users] PMF, Enthalpy, Entropy

[Alex]

Hello all,

I have the calculated the PMF for the adsorption of a peptide into a solid
surface using umbrella sampling, a 60 ns of NVT-production for each window
was considered so that the PMF is well converged.
Now, following a nice paper by Prof. van der Spoel "*DOI: *10.1021/ct400404q"
and in the same fashion as (Fig.4 of the paper) I also would like to
calculate the enthalpy and entropy along the reaction coordinate of the PMF.

To do so, for each window I calculated the enthalpy via "gmx energy
case.edr ... " and selected "potential" as in the NVT ensemble, enthalpy
and potential are identical. And then using the Gibbs free energy equationI
calculated the "- [T*\Delat S]", so that at the end I have all of three
quantity as a function of the reaction coordinate.

I do not know why the PMF and Enthalpy (potential) are not in the same(or
close) order of magnitude.  The trusted PMF is around "60 kcal/mol=251.0
kj/mol" while the Enthalpy is something like "-1557.92e+03 kj/mol", I was
wondering if the unit of enthalpy (potential) here is really meaningful?
Does the enthalpy's unit is "kj/mol" or "j/mol", as a division to "1000"
could give more sense to it?

I know the convergence of the enthalpy is hard respect to the convergence
of the PMF, but, here the convergence is not the matter, rather the unit of
enthalpy is the matter.

Here is the potential average of enthalpy (potential) for one of the window
via gmx energy:

Energy  Average   Err.Est.   RMSD  Tot-Drift

Potential-1.5579e+06 14726.909-14.203
(kJ/mol)

Which of the "Err,Est" or "Tot-Drift" is the error bar for enthalpy
(potential)?

And finally, what does the "normalization to zero at infinite distance"
means?

Any help is highly appreciated.

Best regards,
Alex
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[gmx-users] PMF simulation in Gromacs 2016.1

[Li, Shi]

Dear Gromacs users,

I am comparing the PMF simulations using the Gromacs 2016 version with old
version 5.0.5. I found the *gmx wham* in Gromacs 5.0.5 couldn't process the
tpr files generated by Gromacs 2016.1 . (tpx version 100 vs. tpx version
110). The new Gromacs 2016.1 can process the tpr files that generated from
Gromacs 5.0.5, but the results are different, most of the energy in the new
output .xvg file is zero, but using the old version to process the same
input files, the resulting .xvg is fine.

While using the Gromacs 2016.1 to process the tpx version 110
files(generated by the new version). The resulting .xvg also shows a lot of
zero energies.

I am not sure where I did wrong or how to fix this problem, any suggestion
will be appreciated.

Thanks.
Shi
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Re: [gmx-users] PMF changing drastically with the number of bins

[Sajeewa Pemasinghe]

Dear all,

I have made mistake. I didn't compare the value of free energy at the
minimum with the plateau value. At all three bin numbers the difference is
close to 2 kCal mol-1.
So this is solved.

Best regards

Sajeewa

On Mon, Dec 19, 2016 at 1:15 PM, Sajeewa Pemasinghe 
wrote:

> Dear all,
>
> I am calculating the PMF as the COM distance of two molecules are changing
> using umbrella sampling ( pull = umbrella ). Each umbrella sampling
> simulation runs for 50ns.  When I calculate the PMF with default (200 bins)
> settings using gmx wham I get the minimum in free energy of -1.19 kCal
> mol-1 at 24.9 Angstrom. When I change the number of bins to 100 the new
> value for minimum is -0.558 kCal mol-1 at 24.8 Angstrom and for 50 bins it
> is -0.195 kCal mol-1 at 24.7 Angstrom. Can the free energy value be this
> much dependent on the number of bins? I suppose the normalization of total
> probability to 1 happens inside the algorithm. Could anyone give me a
> suggestion to this much of a variation?
>
> Best regards
>
> Sajeewa
>
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[gmx-users] PMF changing drastically with the number of bins

[Sajeewa Pemasinghe]

Dear all,

I am calculating the PMF as the COM distance of two molecules are changing
using umbrella sampling ( pull = umbrella ). Each umbrella sampling
simulation runs for 50ns.  When I calculate the PMF with default (200 bins)
settings using gmx wham I get the minimum in free energy of -1.19 kCal
mol-1 at 24.9 Angstrom. When I change the number of bins to 100 the new
value for minimum is -0.558 kCal mol-1 at 24.8 Angstrom and for 50 bins it
is -0.195 kCal mol-1 at 24.7 Angstrom. Can the free energy value be this
much dependent on the number of bins? I suppose the normalization of total
probability to 1 happens inside the algorithm. Could anyone give me a
suggestion to this much of a variation?

Best regards

Sajeewa
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Re: [gmx-users] PMF decompostion

[Justin Lemkul]

er: http://pubs.acs.org/doi/abs/10.1021/ct400404q




From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se <
gromacs.org_gmx-users-boun...@maillist.sys.kth.se> on behalf of Salman
Zarrini <salman.zarr...@gmail.com>
Sent: 02 December 2016 17:16:15
To: gmx-us...@gromacs.org
Subject: [gmx-users] PMF decompostion

Dear gromacs user,

I was wondering if something has been already implemented in gromacs to
make possible the potential of mean force (PMF) decomposition into the
van
der waals and electrostatic energies?

Would you please also let me know if the desolvation energy originated
from
protein-water or in my case solid surface-water interaction, will be
taken
into account automatically when one calculates the PMF in aqueous
solution
in gromacs?

Thanks.

Cheers,
Salman Zarrini
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--
David van der Spoel, Ph.D., Professor of Biology
Dept. of Cell & Molec. Biol., Uppsala University.
Box 596, 75124 Uppsala, Sweden. Phone:  +46184714205.
sp...@xray.bmc.uu.sehttp://folding.bmc.uu.se

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--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==

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--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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Re: [gmx-users] PMF decompostion

[Salman Zarrini]

If the force field is the issue, then, I would say the decomposition of
free energy in the perturbation based methods like alchemical is
meaningless as well, however, there are bunch of published works reporting
the evolution of free energy based on their contributors coupling
parameters, \lambda_{elec}, \lambda_{vdW} ... .

No comment on desolvation energy, please?
If the desolvation energy originated from protein-water or in my case solid
surface-water interaction, will be taken into account automatically when
one calculates the free energy in aqueous solution by PMF or FEP in gromacs?

Thanks,

Salman Zarrini


On Mon, Dec 5, 2016 at 12:07 AM, Justin Lemkul <jalem...@vt.edu> wrote:

>
>
> On 12/3/16 10:29 AM, Salman Zarrini wrote:
>
>> Thanks David and Christopher for your responses.
>>
>> I do not understand why vdW and Q are not meaningful contributors of PMF
>> as
>> a biasing method, as I think one can loop over the trajectory of all the
>> biasing method either from US or Metadynamics and recompute the force
>> separating vdW and electrostatic and then project them on to the reaction
>> coordinate ... ,  after doing a little math, averaging, integration and
>> scripting you have the portion of each energy.
>>
>>
> These are force field quantities, not real physical quantities.  Depending
> on how the force field was parametrized, decomposing the total energy may
> be completely unphysical and therefore useless.  Sometimes inclusion of a
> term in vdW is a compensation for inadequate electrostatic representations
> and/or deficiencies in LJ combination rules.  Take, for a simple example,
> NBFIX in CHARMM between ions.  There is no way to change the ion parameters
> in the additive force field (they have to be, e.g. +1 or -1 charge), and
> their LJ reproduce individual ion hydration free energies, so we mitigate
> overly attractive cation-anion interactions in some cases by modifying LJ
> specifically for their interaction while leaving ion-water interactions
> (default combination rules) alone.
>
> So, sure, you can recompute and/or decompose these energies, but they
> don't necessarily mean anything.
>
> -Justin
>
>
> Concerning to the entropy and enthalpy portions, I am using covar and
>> anaeig to calculate eigenvectors over "non-water" ingredients for both
>> analyzing and fitting,  and then quasihamonic approximation and
>> Schlitter's
>> formula for the entropy, but the problem is that, already the difference
>> between the entropy out of these two methods is something around "43 kcal/
>> mol" in each windows, if this is normal?
>> Both analyzing and fitting are "non-mass wighted" in my calculations.
>> Do you think I should get something close to the entropy of the
>> quasihamonic approximation Schlitter's formula if I use the method
>> proposed
>> by you?
>>
>> Cheers,
>>
>> Salman Zarrini
>>
>>
>>
>> On Sat, Dec 3, 2016 at 7:19 AM, David van der Spoel <sp...@xray.bmc.uu.se
>> >
>> wrote:
>>
>> On 02/12/16 23:40, Christopher Neale wrote:
>>>
>>> PMF gives free energy, which can not be decomposed into VDW and Q without
>>>> leaving a remainder, though I guess that doesn't affect your question.
>>>> Enthalpy is simply the average potential energy plus the pressure volume
>>>> component. So you can compute average potential energy VDW and Q
>>>> components
>>>> at each umbrella if you want (from the .edr files with gmx energy). Be
>>>> aware that the statistical uncertainty on the enthalpy tends to be
>>>> greater
>>>> than the relevant differences on achievable simulation timescales (i.e.,
>>>> convergence is hard), so you'll want to evaluate error explicitly.
>>>>
>>>> Agree with Chris here, that enthalpy and entropy are the
>>>>
>>> thermodynamically meaningful components here. VDW and Q does not mean
>>> anything outside the force field definition since they can not be
>>> measured
>>> in any way. For more info on decomposing into enthalpy and entropy, see
>>> this paper: http://pubs.acs.org/doi/abs/10.1021/ct400404q
>>>
>>> 
>>>
>>>> From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se <
>>>> gromacs.org_gmx-users-boun...@maillist.sys.kth.se> on behalf of Salman
>>>> Zarrini <salman.zarr...@gmail.com>
>>>> Sent: 02 December 2016 17:16:15
>>>> To: gmx-us...@gromacs.org
>>>> Subject: [gmx-users] PMF decompostion
>&

Re: [gmx-users] PMF decompostion

[Justin Lemkul]

On 12/3/16 10:29 AM, Salman Zarrini wrote:

Thanks David and Christopher for your responses.

I do not understand why vdW and Q are not meaningful contributors of PMF as
a biasing method, as I think one can loop over the trajectory of all the
biasing method either from US or Metadynamics and recompute the force
separating vdW and electrostatic and then project them on to the reaction
coordinate ... ,  after doing a little math, averaging, integration and
scripting you have the portion of each energy.



These are force field quantities, not real physical quantities.  Depending on 
how the force field was parametrized, decomposing the total energy may be 
completely unphysical and therefore useless.  Sometimes inclusion of a term in 
vdW is a compensation for inadequate electrostatic representations and/or 
deficiencies in LJ combination rules.  Take, for a simple example, NBFIX in 
CHARMM between ions.  There is no way to change the ion parameters in the 
additive force field (they have to be, e.g. +1 or -1 charge), and their LJ 
reproduce individual ion hydration free energies, so we mitigate overly 
attractive cation-anion interactions in some cases by modifying LJ specifically 
for their interaction while leaving ion-water interactions (default combination 
rules) alone.


So, sure, you can recompute and/or decompose these energies, but they don't 
necessarily mean anything.


-Justin


Concerning to the entropy and enthalpy portions, I am using covar and
anaeig to calculate eigenvectors over "non-water" ingredients for both
analyzing and fitting,  and then quasihamonic approximation and Schlitter's
formula for the entropy, but the problem is that, already the difference
between the entropy out of these two methods is something around "43 kcal/
mol" in each windows, if this is normal?
Both analyzing and fitting are "non-mass wighted" in my calculations.
Do you think I should get something close to the entropy of the
quasihamonic approximation Schlitter's formula if I use the method proposed
by you?

Cheers,

Salman Zarrini



On Sat, Dec 3, 2016 at 7:19 AM, David van der Spoel <sp...@xray.bmc.uu.se>
wrote:


On 02/12/16 23:40, Christopher Neale wrote:


PMF gives free energy, which can not be decomposed into VDW and Q without
leaving a remainder, though I guess that doesn't affect your question.
Enthalpy is simply the average potential energy plus the pressure volume
component. So you can compute average potential energy VDW and Q components
at each umbrella if you want (from the .edr files with gmx energy). Be
aware that the statistical uncertainty on the enthalpy tends to be greater
than the relevant differences on achievable simulation timescales (i.e.,
convergence is hard), so you'll want to evaluate error explicitly.

Agree with Chris here, that enthalpy and entropy are the

thermodynamically meaningful components here. VDW and Q does not mean
anything outside the force field definition since they can not be measured
in any way. For more info on decomposing into enthalpy and entropy, see
this paper: http://pubs.acs.org/doi/abs/10.1021/ct400404q



From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se <
gromacs.org_gmx-users-boun...@maillist.sys.kth.se> on behalf of Salman
Zarrini <salman.zarr...@gmail.com>
Sent: 02 December 2016 17:16:15
To: gmx-us...@gromacs.org
Subject: [gmx-users] PMF decompostion

Dear gromacs user,

I was wondering if something has been already implemented in gromacs to
make possible the potential of mean force (PMF) decomposition into the van
der waals and electrostatic energies?

Would you please also let me know if the desolvation energy originated
from
protein-water or in my case solid surface-water interaction, will be taken
into account automatically when one calculates the PMF in aqueous solution
in gromacs?

Thanks.

Cheers,
Salman Zarrini
--
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* Please search the archive at http://www.gromacs.org/Support
/Mailing_Lists/GMX-Users_List before posting!

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--
David van der Spoel, Ph.D., Professor of Biology
Dept. of Cell & Molec. Biol., Uppsala University.
Box 596, 75124 Uppsala, Sweden. Phone:  +46184714205.
sp...@xray.bmc.uu.sehttp://folding.bmc.uu.se

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--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral 

Re: [gmx-users] PMF decompostion

[Salman Zarrini]

Thanks David and Christopher for your responses.

I do not understand why vdW and Q are not meaningful contributors of PMF as
a biasing method, as I think one can loop over the trajectory of all the
biasing method either from US or Metadynamics and recompute the force
separating vdW and electrostatic and then project them on to the reaction
coordinate ... ,  after doing a little math, averaging, integration and
scripting you have the portion of each energy.

Concerning to the entropy and enthalpy portions, I am using covar and
anaeig to calculate eigenvectors over "non-water" ingredients for both
analyzing and fitting,  and then quasihamonic approximation and Schlitter's
formula for the entropy, but the problem is that, already the difference
between the entropy out of these two methods is something around "43 kcal/
mol" in each windows, if this is normal?
Both analyzing and fitting are "non-mass wighted" in my calculations.
Do you think I should get something close to the entropy of the
quasihamonic approximation Schlitter's formula if I use the method proposed
by you?

Cheers,

Salman Zarrini



On Sat, Dec 3, 2016 at 7:19 AM, David van der Spoel <sp...@xray.bmc.uu.se>
wrote:

> On 02/12/16 23:40, Christopher Neale wrote:
>
>> PMF gives free energy, which can not be decomposed into VDW and Q without
>> leaving a remainder, though I guess that doesn't affect your question.
>> Enthalpy is simply the average potential energy plus the pressure volume
>> component. So you can compute average potential energy VDW and Q components
>> at each umbrella if you want (from the .edr files with gmx energy). Be
>> aware that the statistical uncertainty on the enthalpy tends to be greater
>> than the relevant differences on achievable simulation timescales (i.e.,
>> convergence is hard), so you'll want to evaluate error explicitly.
>>
>> Agree with Chris here, that enthalpy and entropy are the
> thermodynamically meaningful components here. VDW and Q does not mean
> anything outside the force field definition since they can not be measured
> in any way. For more info on decomposing into enthalpy and entropy, see
> this paper: http://pubs.acs.org/doi/abs/10.1021/ct400404q
>
> 
>> From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se <
>> gromacs.org_gmx-users-boun...@maillist.sys.kth.se> on behalf of Salman
>> Zarrini <salman.zarr...@gmail.com>
>> Sent: 02 December 2016 17:16:15
>> To: gmx-us...@gromacs.org
>> Subject: [gmx-users] PMF decompostion
>>
>> Dear gromacs user,
>>
>> I was wondering if something has been already implemented in gromacs to
>> make possible the potential of mean force (PMF) decomposition into the van
>> der waals and electrostatic energies?
>>
>> Would you please also let me know if the desolvation energy originated
>> from
>> protein-water or in my case solid surface-water interaction, will be taken
>> into account automatically when one calculates the PMF in aqueous solution
>> in gromacs?
>>
>> Thanks.
>>
>> Cheers,
>> Salman Zarrini
>> --
>> Gromacs Users mailing list
>>
>> * Please search the archive at http://www.gromacs.org/Support
>> /Mailing_Lists/GMX-Users_List before posting!
>>
>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>
>> * For (un)subscribe requests visit
>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
>> send a mail to gmx-users-requ...@gromacs.org.
>>
>>
>
> --
> David van der Spoel, Ph.D., Professor of Biology
> Dept. of Cell & Molec. Biol., Uppsala University.
> Box 596, 75124 Uppsala, Sweden. Phone:  +46184714205.
> sp...@xray.bmc.uu.sehttp://folding.bmc.uu.se
>
> --
> Gromacs Users mailing list
>
> * Please search the archive at http://www.gromacs.org/Support
> /Mailing_Lists/GMX-Users_List before posting!
>
> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>
> * For (un)subscribe requests visit
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> send a mail to gmx-users-requ...@gromacs.org.
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Re: [gmx-users] PMF decompostion

[David van der Spoel]

On 02/12/16 23:40, Christopher Neale wrote:

PMF gives free energy, which can not be decomposed into VDW and Q without 
leaving a remainder, though I guess that doesn't affect your question. Enthalpy 
is simply the average potential energy plus the pressure volume component. So 
you can compute average potential energy VDW and Q components at each umbrella 
if you want (from the .edr files with gmx energy). Be aware that the 
statistical uncertainty on the enthalpy tends to be greater than the relevant 
differences on achievable simulation timescales (i.e., convergence is hard), so 
you'll want to evaluate error explicitly.

Agree with Chris here, that enthalpy and entropy are the 
thermodynamically meaningful components here. VDW and Q does not mean 
anything outside the force field definition since they can not be 
measured in any way. For more info on decomposing into enthalpy and 
entropy, see this paper: http://pubs.acs.org/doi/abs/10.1021/ct400404q




From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se 
<gromacs.org_gmx-users-boun...@maillist.sys.kth.se> on behalf of Salman Zarrini 
<salman.zarr...@gmail.com>
Sent: 02 December 2016 17:16:15
To: gmx-us...@gromacs.org
Subject: [gmx-users] PMF decompostion

Dear gromacs user,

I was wondering if something has been already implemented in gromacs to
make possible the potential of mean force (PMF) decomposition into the van
der waals and electrostatic energies?

Would you please also let me know if the desolvation energy originated from
protein-water or in my case solid surface-water interaction, will be taken
into account automatically when one calculates the PMF in aqueous solution
in gromacs?

Thanks.

Cheers,
Salman Zarrini
--
Gromacs Users mailing list

* Please search the archive at 
http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting!

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* For (un)subscribe requests visit
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--
David van der Spoel, Ph.D., Professor of Biology
Dept. of Cell & Molec. Biol., Uppsala University.
Box 596, 75124 Uppsala, Sweden. Phone:  +46184714205.
sp...@xray.bmc.uu.sehttp://folding.bmc.uu.se
--
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Re: [gmx-users] PMF decompostion

[Christopher Neale]

PMF gives free energy, which can not be decomposed into VDW and Q without 
leaving a remainder, though I guess that doesn't affect your question. Enthalpy 
is simply the average potential energy plus the pressure volume component. So 
you can compute average potential energy VDW and Q components at each umbrella 
if you want (from the .edr files with gmx energy). Be aware that the 
statistical uncertainty on the enthalpy tends to be greater than the relevant 
differences on achievable simulation timescales (i.e., convergence is hard), so 
you'll want to evaluate error explicitly.


From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se 
<gromacs.org_gmx-users-boun...@maillist.sys.kth.se> on behalf of Salman Zarrini 
<salman.zarr...@gmail.com>
Sent: 02 December 2016 17:16:15
To: gmx-us...@gromacs.org
Subject: [gmx-users] PMF decompostion

Dear gromacs user,

I was wondering if something has been already implemented in gromacs to
make possible the potential of mean force (PMF) decomposition into the van
der waals and electrostatic energies?

Would you please also let me know if the desolvation energy originated from
protein-water or in my case solid surface-water interaction, will be taken
into account automatically when one calculates the PMF in aqueous solution
in gromacs?

Thanks.

Cheers,
Salman Zarrini
--
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* Please search the archive at 
http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting!

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[gmx-users] PMF decompostion

[Salman Zarrini]

Dear gromacs user,

I was wondering if something has been already implemented in gromacs to
make possible the potential of mean force (PMF) decomposition into the van
der waals and electrostatic energies?

Would you please also let me know if the desolvation energy originated from
protein-water or in my case solid surface-water interaction, will be taken
into account automatically when one calculates the PMF in aqueous solution
in gromacs?

Thanks.

Cheers,
Salman Zarrini
-- 
Gromacs Users mailing list

* Please search the archive at 
http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting!

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Re: [gmx-users] pmf settings

[Justin Lemkul]

On 11/17/16 5:33 AM, Qasim Pars wrote:

Dear users,

I am trying to calculate the binding free energy between protein and ligand
using the PMF. I will add the below pull code lines to my production run
mdp file.

pull= umbrella
pull_geometry   = distance
pull_dim= Y Y Y
pull_start  = yes
pull_ngroups= 2
pull_group0 = protein
pull_group1 = ligand
pull_init1  = 0
pull_rate1  = 0.0
pull_k1 = 5000
pull_nstxout= 1000
pull_nstfout= 1000

My questions are:

-According to the above lines the binding free energy is calculated for the
center of mass of each group, right?



The binding free energy is calculated as a function of the reaction coordinate 
defined by the respective centers of mass.  You don't calculate a free energy of 
a center of mass.



-Is it necessary to add the above lines in the nvt.mdp and npt.mdp file as
well?


Yes, equilibrate under the conditions you want to simulate.  If you don't, the 
separation between the protein and ligand will vary, and your use of "pull_start 
= yes" and "pull_init1 = 0" may not mean what you want it to by the time you get 
to production because things will have moved around.




-how can I set/change the number of windows used in the Umbrella Sampling
calculations?



These are all just independent simulations.  See my tutorial for an example:

http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/index.html


-To get the accurate binding energy should I use some specific atoms of
each group (for instance: ligand N1 and protein C15) or the center of mass
of each group?



No.  You may bias the result even more and potentially inhibit sampling.

-Justin

--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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[gmx-users] pmf settings

[Qasim Pars]

Dear users,

I am trying to calculate the binding free energy between protein and ligand
using the PMF. I will add the below pull code lines to my production run
mdp file.

pull= umbrella
pull_geometry   = distance
pull_dim= Y Y Y
pull_start  = yes
pull_ngroups= 2
pull_group0 = protein
pull_group1 = ligand
pull_init1  = 0
pull_rate1  = 0.0
pull_k1 = 5000
pull_nstxout= 1000
pull_nstfout= 1000

My questions are:

-According to the above lines the binding free energy is calculated for the
center of mass of each group, right?

-Is it necessary to add the above lines in the nvt.mdp and npt.mdp file as
well?

-how can I set/change the number of windows used in the Umbrella Sampling
calculations?

-To get the accurate binding energy should I use some specific atoms of
each group (for instance: ligand N1 and protein C15) or the center of mass
of each group?

Hope someone will answer the questions.

Cheers,
-- 
Qasim Pars
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Re: [gmx-users] pmf

[Justin Lemkul]

On 10/28/16 4:20 PM, Alex wrote:

Thanks for your response.
The version for all tasks is "gmx, VERSION 5.1.2".

I hope extra windows would be required just in the gaps, not in the whole
reaction path.


Yes, you just need more windows.


I had 81 windows spacing mostly 0.01 nm and in the end 0.04 nm.



Your histograms indicate that you're not achieving this.  You're getting 
clusters of sampling with gaps.  A resolution of 0.01 nm is probably overkill 
for just about any sort of reaction coordinate; check what grompp tells you 
about each of these starting configurations because it appears you may not be 
getting what you think you are to start.  You have a ton of overlap (i.e., 
redundant sampling) in the histograms.



The peptide surly has many rotations from top of the surface to the midd
point of box where if free of solid surface, I was wondering if this PMF
(which is COM N N Y) has already taken into account all that rotation, if
not, how one can consider these changes?



You have to have converged sampling of all motions.  That requires sufficient 
time and an assessment of how well the PMF itself has converged over time.  You 
don't yet even have a reasonable PMF.


-Justin


Best regards,
Alex


On Fri, Oct 28, 2016 at 10:09 PM, Justin Lemkul  wrote:




On 10/28/16 4:04 PM, Alex wrote:


Dear Gromacs user,

Below are the result of PMF simulation of a peptide adsorbed into a solid
surface.
Would you please comment on them in order to improve the result.

The force constant in the umberela sampling is 1100.
For each windows:  1.2 ns NVT equilibration followed by 2 ns of NPT and 15
ns of NVT produciton run.
Should I change the force constant or increase the simulation time for
each
windows or just increasing the sampling in some region?


https://drive.google.com/open?id=0B_CbyhnbKqQDMkpLc0didlMxTWs

https://drive.google.com/open?id=0B_CbyhnbKqQDZ1RpT3JxMjdyazA



You need more windows.  You have obvious gaps in several parts of the
reaction coordinate.

https://drive.google.com/open?id=0B_CbyhnbKqQDZlR4RGVIWk5KbVU


It is just one dimension pulling by "N N Y" by pull-coord1-geometry =
distance, then I was also wondeing why my pullx.xvg files has more than
normal column so that gmx wham complain with error about it:
Fatal error:
Using 1 pull coodinates from prdd.0.tpr,
 but found 4 data columns in pullx-prd.0.xvg (expected 3).



What version of GROMACS is this?  Is the version of gmx wham the same as
the version of grompp/mdrun used to create/run the simulations?  I would
expect 4 as well (COM x,y,z of reference and z-coordinate of pulled group),
but there have been a lot of changes to the pull code in recent versions.

-Justin

--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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Re: [gmx-users] pmf

[Alex]

Thanks for your response.
The version for all tasks is "gmx, VERSION 5.1.2".

I hope extra windows would be required just in the gaps, not in the whole
reaction path.
I had 81 windows spacing mostly 0.01 nm and in the end 0.04 nm.

The peptide surly has many rotations from top of the surface to the midd
point of box where if free of solid surface, I was wondering if this PMF
(which is COM N N Y) has already taken into account all that rotation, if
not, how one can consider these changes?

Best regards,
Alex


On Fri, Oct 28, 2016 at 10:09 PM, Justin Lemkul  wrote:

>
>
> On 10/28/16 4:04 PM, Alex wrote:
>
>> Dear Gromacs user,
>>
>> Below are the result of PMF simulation of a peptide adsorbed into a solid
>> surface.
>> Would you please comment on them in order to improve the result.
>>
>> The force constant in the umberela sampling is 1100.
>> For each windows:  1.2 ns NVT equilibration followed by 2 ns of NPT and 15
>> ns of NVT produciton run.
>> Should I change the force constant or increase the simulation time for
>> each
>> windows or just increasing the sampling in some region?
>>
>>
>> https://drive.google.com/open?id=0B_CbyhnbKqQDMkpLc0didlMxTWs
>>
>> https://drive.google.com/open?id=0B_CbyhnbKqQDZ1RpT3JxMjdyazA
>>
>>
> You need more windows.  You have obvious gaps in several parts of the
> reaction coordinate.
>
> https://drive.google.com/open?id=0B_CbyhnbKqQDZlR4RGVIWk5KbVU
>>
>> It is just one dimension pulling by "N N Y" by pull-coord1-geometry =
>> distance, then I was also wondeing why my pullx.xvg files has more than
>> normal column so that gmx wham complain with error about it:
>> Fatal error:
>> Using 1 pull coodinates from prdd.0.tpr,
>>  but found 4 data columns in pullx-prd.0.xvg (expected 3).
>>
>>
> What version of GROMACS is this?  Is the version of gmx wham the same as
> the version of grompp/mdrun used to create/run the simulations?  I would
> expect 4 as well (COM x,y,z of reference and z-coordinate of pulled group),
> but there have been a lot of changes to the pull code in recent versions.
>
> -Justin
>
> --
> ==
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 629
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> jalem...@outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
> ==
> --
> Gromacs Users mailing list
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> * Please search the archive at http://www.gromacs.org/Support
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Re: [gmx-users] pmf

[Justin Lemkul]

On 10/28/16 4:04 PM, Alex wrote:

Dear Gromacs user,

Below are the result of PMF simulation of a peptide adsorbed into a solid
surface.
Would you please comment on them in order to improve the result.

The force constant in the umberela sampling is 1100.
For each windows:  1.2 ns NVT equilibration followed by 2 ns of NPT and 15
ns of NVT produciton run.
Should I change the force constant or increase the simulation time for each
windows or just increasing the sampling in some region?


https://drive.google.com/open?id=0B_CbyhnbKqQDMkpLc0didlMxTWs

https://drive.google.com/open?id=0B_CbyhnbKqQDZ1RpT3JxMjdyazA



You need more windows.  You have obvious gaps in several parts of the reaction 
coordinate.



https://drive.google.com/open?id=0B_CbyhnbKqQDZlR4RGVIWk5KbVU

It is just one dimension pulling by "N N Y" by pull-coord1-geometry =
distance, then I was also wondeing why my pullx.xvg files has more than
normal column so that gmx wham complain with error about it:
Fatal error:
Using 1 pull coodinates from prdd.0.tpr,
 but found 4 data columns in pullx-prd.0.xvg (expected 3).



What version of GROMACS is this?  Is the version of gmx wham the same as the 
version of grompp/mdrun used to create/run the simulations?  I would expect 4 as 
well (COM x,y,z of reference and z-coordinate of pulled group), but there have 
been a lot of changes to the pull code in recent versions.


-Justin

--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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[gmx-users] pmf

[Alex]

Dear Gromacs user,

Below are the result of PMF simulation of a peptide adsorbed into a solid
surface.
Would you please comment on them in order to improve the result.

The force constant in the umberela sampling is 1100.
For each windows:  1.2 ns NVT equilibration followed by 2 ns of NPT and 15
ns of NVT produciton run.
Should I change the force constant or increase the simulation time for each
windows or just increasing the sampling in some region?


https://drive.google.com/open?id=0B_CbyhnbKqQDMkpLc0didlMxTWs

https://drive.google.com/open?id=0B_CbyhnbKqQDZ1RpT3JxMjdyazA

https://drive.google.com/open?id=0B_CbyhnbKqQDZlR4RGVIWk5KbVU

It is just one dimension pulling by "N N Y" by pull-coord1-geometry =
distance, then I was also wondeing why my pullx.xvg files has more than
normal column so that gmx wham complain with error about it:
Fatal error:
Using 1 pull coodinates from prdd.0.tpr,
 but found 4 data columns in pullx-prd.0.xvg (expected 3).

Thanks very much in advance.

Regards,
Alex
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Re: [gmx-users] PMF

[Alex]

The negative and positive in the the reaction coordinate comes probably
from interaction of peptide with surface in bottom slab and top(next cell
beacuse of PBC) slab in the Z direction.
But I was always taking care about sampled windows so that the peptide
pulled away from top of bottom surface to the midd point of box out of cut
of and all the sampled windows was chosen from the bottom part of the box.,
and this means no interaction it should have with the top slab in the next
cell.

---  > top slab



  > midd of box
}
} -> 39 Sampled windows
}
---  > Bottom slab


Regards,
Alex

On Thu, Oct 13, 2016 at 2:09 PM, Justin Lemkul  wrote:

>
>
> On 10/13/16 5:28 AM, Alex wrote:
>
>> Thanks for your response.
>>
>> Actually I fully followed your tutorial. the pull-coord1-rate = 0.007
>> indicated in the pdf file is just for the pulling step and then in the
>> next
>> step I have  pull-coord1-rate = 0.0 for each windows. Can we do the
>> pulling
>> step with pull-coord1-rate = 0.0 !?
>>
>>
> No, that would accomplish nothing.  To cause a net displacement, you must
> have a non-zero pulling rate.  To do umbrella sampling, you need a zero
> pulling rate.
>
> Your histograms indicate that you have sampling at both positive and
> negative values along the reaction coordinate.  For a simple pull away from
> a surface, there should be no sign change.  So you have some sort of
> artificial behavior, e.g. jump across a periodic boundary, that is throwing
> off your whole PMF.
>
> -Justin
>
>
> Regards,
>> Alex
>>
>> On Thu, Oct 13, 2016 at 12:02 AM, Justin Lemkul  wrote:
>>
>>
>>>
>>> On 10/11/16 4:01 PM, Alex wrote:
>>>
>>> Dear gromacs user,

 I am trying to simulate the PMF a small peptide adsorbed to a solid
 surface
 but no success unfurtunatly.
 For some force constant the peptide would not desorbed from the surface
 and
 for higher force constants what you can see in enclosed file will
 happen.
 Some question is:
 If it is possible to somehow change the force constant for a coordinate
 while pulling step? for example the first 1 ns by by k1 = 5000 and then
 reduced to k1 = 1000 for the rest of pulling.


 gmx wham won't account for changes in k over time.  But you can use
>>> different force constants in different windows; that's fine.
>>>
>>> Also, the force constant in the pulling step and umbrella sampling do not
>>>
 need to be the same necessarily?


 Correct.
>>>
>>> How I can improve or increase the number of sampled frame?
>>>

  I have enclosed some results as well as mdp file and force in pulling
 step
 in each step below, I would be so appreciated if you could guide me to
 improve the results?

 PMF result:
 https://drive.google.com/open?id=0B_CbyhnbKqQDMC1Ua3BWLUZ3XzA


 If you have a non-zero pulling rate (which you have specified above),
>>> you're not doing umbrella sampling, you're doing non-equilibrium SMD.  So
>>> this PMF is junk.  You need to have multiple windows, each with a set
>>> reference restraint distance, and a zero pull rate so the conformations
>>> can
>>> oscillate about that reference length.
>>>
>>> -Justin
>>>
>>> Force in pulling SMD
>>>
 https://drive.google.com/open?id=0B_CbyhnbKqQDVWxkd2VLUmozUjg

 position in pulling SMD
 https://drive.google.com/open?id=0B_CbyhnbKqQDa0VKX0E0Zlp1ODA

 Windows-com
 https://drive.google.com/open?id=0B_CbyhnbKqQDR0poVlM2RTVSNG8

 md-production.mdp
 https://drive.google.com/open?id=0B_CbyhnbKqQDdGFRbWQzb29Nbmc

 md-pulling.mdp
 https://drive.google.com/open?id=0B_CbyhnbKqQDc2NPdlVmSmwydFk

 nvt-umbrella.mdp
 https://drive.google.com/open?id=0B_CbyhnbKqQDSk9LS2d2Q1pTN2s

 npt-umbrella.mdp
 https://drive.google.com/open?id=0B_CbyhnbKqQDVnB4STFxeENfREU

 md-umbrella.mdp
 https://drive.google.com/open?id=0B_CbyhnbKqQDQmFTZWRkR1BkcUE

 Thank you very much in advance.

 Regards,
 Alex


 --
>>> ==
>>>
>>> Justin A. Lemkul, Ph.D.
>>> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>>>
>>> Department of Pharmaceutical Sciences
>>> School of Pharmacy
>>> Health Sciences Facility II, Room 629
>>> University of Maryland, Baltimore
>>> 20 Penn St.
>>> Baltimore, MD 21201
>>>
>>> jalem...@outerbanks.umaryland.edu | (410) 706-7441
>>> http://mackerell.umaryland.edu/~jalemkul
>>>
>>> ==
>>> --
>>> Gromacs Users mailing list
>>>
>>> * Please search the archive at http://www.gromacs.org/Support
>>> /Mailing_Lists/GMX-Users_List before posting!
>>>
>>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>>

Re: [gmx-users] PMF

[Alex]

Thanks for your response.

Actually I fully followed your tutorial. the pull-coord1-rate = 0.007
indicated in the pdf file is just for the pulling step and then in the next
step I have  pull-coord1-rate = 0.0 for each windows. Can we do the pulling
step with pull-coord1-rate = 0.0 !?

Regards,
Alex

On Thu, Oct 13, 2016 at 12:02 AM, Justin Lemkul  wrote:

>
>
> On 10/11/16 4:01 PM, Alex wrote:
>
>> Dear gromacs user,
>>
>> I am trying to simulate the PMF a small peptide adsorbed to a solid
>> surface
>> but no success unfurtunatly.
>> For some force constant the peptide would not desorbed from the surface
>> and
>> for higher force constants what you can see in enclosed file will happen.
>> Some question is:
>> If it is possible to somehow change the force constant for a coordinate
>> while pulling step? for example the first 1 ns by by k1 = 5000 and then
>> reduced to k1 = 1000 for the rest of pulling.
>>
>>
> gmx wham won't account for changes in k over time.  But you can use
> different force constants in different windows; that's fine.
>
> Also, the force constant in the pulling step and umbrella sampling do not
>> need to be the same necessarily?
>>
>>
> Correct.
>
> How I can improve or increase the number of sampled frame?
>>
>>  I have enclosed some results as well as mdp file and force in pulling
>> step
>> in each step below, I would be so appreciated if you could guide me to
>> improve the results?
>>
>> PMF result:
>> https://drive.google.com/open?id=0B_CbyhnbKqQDMC1Ua3BWLUZ3XzA
>>
>>
> If you have a non-zero pulling rate (which you have specified above),
> you're not doing umbrella sampling, you're doing non-equilibrium SMD.  So
> this PMF is junk.  You need to have multiple windows, each with a set
> reference restraint distance, and a zero pull rate so the conformations can
> oscillate about that reference length.
>
> -Justin
>
> Force in pulling SMD
>> https://drive.google.com/open?id=0B_CbyhnbKqQDVWxkd2VLUmozUjg
>>
>> position in pulling SMD
>> https://drive.google.com/open?id=0B_CbyhnbKqQDa0VKX0E0Zlp1ODA
>>
>> Windows-com
>> https://drive.google.com/open?id=0B_CbyhnbKqQDR0poVlM2RTVSNG8
>>
>> md-production.mdp
>> https://drive.google.com/open?id=0B_CbyhnbKqQDdGFRbWQzb29Nbmc
>>
>> md-pulling.mdp
>> https://drive.google.com/open?id=0B_CbyhnbKqQDc2NPdlVmSmwydFk
>>
>> nvt-umbrella.mdp
>> https://drive.google.com/open?id=0B_CbyhnbKqQDSk9LS2d2Q1pTN2s
>>
>> npt-umbrella.mdp
>> https://drive.google.com/open?id=0B_CbyhnbKqQDVnB4STFxeENfREU
>>
>> md-umbrella.mdp
>> https://drive.google.com/open?id=0B_CbyhnbKqQDQmFTZWRkR1BkcUE
>>
>> Thank you very much in advance.
>>
>> Regards,
>> Alex
>>
>>
> --
> ==
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 629
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> jalem...@outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
> ==
> --
> Gromacs Users mailing list
>
> * Please search the archive at http://www.gromacs.org/Support
> /Mailing_Lists/GMX-Users_List before posting!
>
> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>
> * For (un)subscribe requests visit
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> send a mail to gmx-users-requ...@gromacs.org.
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Re: [gmx-users] PMF

[Justin Lemkul]

On 10/11/16 4:01 PM, Alex wrote:

Dear gromacs user,

I am trying to simulate the PMF a small peptide adsorbed to a solid surface
but no success unfurtunatly.
For some force constant the peptide would not desorbed from the surface and
for higher force constants what you can see in enclosed file will happen.
Some question is:
If it is possible to somehow change the force constant for a coordinate
while pulling step? for example the first 1 ns by by k1 = 5000 and then
reduced to k1 = 1000 for the rest of pulling.



gmx wham won't account for changes in k over time.  But you can use different 
force constants in different windows; that's fine.



Also, the force constant in the pulling step and umbrella sampling do not
need to be the same necessarily?



Correct.


How I can improve or increase the number of sampled frame?

 I have enclosed some results as well as mdp file and force in pulling step
in each step below, I would be so appreciated if you could guide me to
improve the results?

PMF result:
https://drive.google.com/open?id=0B_CbyhnbKqQDMC1Ua3BWLUZ3XzA



If you have a non-zero pulling rate (which you have specified above), you're not 
doing umbrella sampling, you're doing non-equilibrium SMD.  So this PMF is junk. 
 You need to have multiple windows, each with a set reference restraint 
distance, and a zero pull rate so the conformations can oscillate about that 
reference length.


-Justin


Force in pulling SMD
https://drive.google.com/open?id=0B_CbyhnbKqQDVWxkd2VLUmozUjg

position in pulling SMD
https://drive.google.com/open?id=0B_CbyhnbKqQDa0VKX0E0Zlp1ODA

Windows-com
https://drive.google.com/open?id=0B_CbyhnbKqQDR0poVlM2RTVSNG8

md-production.mdp
https://drive.google.com/open?id=0B_CbyhnbKqQDdGFRbWQzb29Nbmc

md-pulling.mdp
https://drive.google.com/open?id=0B_CbyhnbKqQDc2NPdlVmSmwydFk

nvt-umbrella.mdp
https://drive.google.com/open?id=0B_CbyhnbKqQDSk9LS2d2Q1pTN2s

npt-umbrella.mdp
https://drive.google.com/open?id=0B_CbyhnbKqQDVnB4STFxeENfREU

md-umbrella.mdp
https://drive.google.com/open?id=0B_CbyhnbKqQDQmFTZWRkR1BkcUE

Thank you very much in advance.

Regards,
Alex



--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
--
Gromacs Users mailing list

* Please search the archive at 
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[gmx-users] PMF

[Alex]

Dear gromacs user,

I am trying to simulate the PMF a small peptide adsorbed to a solid surface
but no success unfurtunatly.
For some force constant the peptide would not desorbed from the surface and
for higher force constants what you can see in enclosed file will happen.
Some question is:
If it is possible to somehow change the force constant for a coordinate
while pulling step? for example the first 1 ns by by k1 = 5000 and then
reduced to k1 = 1000 for the rest of pulling.

Also, the force constant in the pulling step and umbrella sampling do not
need to be the same necessarily?

How I can improve or increase the number of sampled frame?

 I have enclosed some results as well as mdp file and force in pulling step
in each step below, I would be so appreciated if you could guide me to
improve the results?

PMF result:
https://drive.google.com/open?id=0B_CbyhnbKqQDMC1Ua3BWLUZ3XzA

Force in pulling SMD
https://drive.google.com/open?id=0B_CbyhnbKqQDVWxkd2VLUmozUjg

position in pulling SMD
https://drive.google.com/open?id=0B_CbyhnbKqQDa0VKX0E0Zlp1ODA

Windows-com
https://drive.google.com/open?id=0B_CbyhnbKqQDR0poVlM2RTVSNG8

md-production.mdp
https://drive.google.com/open?id=0B_CbyhnbKqQDdGFRbWQzb29Nbmc

md-pulling.mdp
https://drive.google.com/open?id=0B_CbyhnbKqQDc2NPdlVmSmwydFk

nvt-umbrella.mdp
https://drive.google.com/open?id=0B_CbyhnbKqQDSk9LS2d2Q1pTN2s

npt-umbrella.mdp
https://drive.google.com/open?id=0B_CbyhnbKqQDVnB4STFxeENfREU

md-umbrella.mdp
https://drive.google.com/open?id=0B_CbyhnbKqQDQmFTZWRkR1BkcUE

Thank you very much in advance.

Regards,
Alex
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Re: [gmx-users] PMF and lack if NPT equilibration

[Alex]

Thanks.

I used the "direction-periodic",  along with "semiisotropic" with zero
compressibility in Z direction to have also NPT equilibration in each
windows. Below is the final pressure after NPT equilibration with 1 bar
reference, I hope it would be ok?!

Energy  Average   Err.Est.   RMSD  Tot-Drift
---
Pressure   -252.127   0.66165.0533.15753  (bar)

Regards,
Alex


On Mon, Oct 10, 2016 at 8:25 PM, Justin Lemkul  wrote:

>
>
> On 10/10/16 4:57 AM, Alex wrote:
>
>> Thanks for your response.
>>
>> My question is not in the sampling step as I have already pulled away two
>> parts and even picked out the configuration of each windows. But my
>> question is about simulation in each individual windows toward WHAM.
>>
>> You means in the step six of the tutorial no necessarily need to do any
>> NVT
>> or NPT before production simulation?
>>
>>
> It's no different from any simulation.  You need to equilibrate under the
> ensemble you're going to use for data collection before you actually do
> that data collection.  If you would normally want NPT for a Gibbs free
> energy and can't get it for whatever reason (like the algorithmic
> limitation mentioned), then equilibrate with NPT to arrive at the desired
> density, and continue with NVT.  You won't get a Gibbs free energy, you'll
> get the Helmholtz free energy, but at least the density will be right.
> Otherwise, build a bigger system that removes the restrictions of
> direction_periodic and use NPT.
>
> -Justin
>
>
> Thanks,
>> Alex
>>
>>
>> On Mon, Oct 10, 2016 at 2:17 AM, Justin Lemkul  wrote:
>>
>>
>>>
>>> On 10/8/16 2:46 PM, Alex wrote:
>>>
>>> Dear gromacs user,

 In a PMF simulation of a short peptide on solid surface, I am using the
 "direction-periodic" as "pull-coord1-geometry" in the Z  direction, then
 as
 you know the equilibration of the system in NPT ensemble is not doable
 for
 the individual windows. So, for each windows of umbrella sampling, I am
 going to do minimization and NVT equilibration and then MD production. I
 was wondering if the lack of the NPT  equilibration would not badly
 affect
 on the result PMF? If so, how can I compensate it somehow?


 All you're doing is sampling under a different ensemble.  There's no
>>> reason to think that a PMF requires an NPT ensemble.
>>>
>>> -Justin
>>>
>>> By the way, I nicely minimized. equilibrated (both NVT and NPT) and a 60
>>> ns
>>>
 of production simulation of my initial system before coming to the
 pulling
 step.

 Thanks.

 Regards,
 Alex


 --
>>> ==
>>>
>>> Justin A. Lemkul, Ph.D.
>>> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>>>
>>> Department of Pharmaceutical Sciences
>>> School of Pharmacy
>>> Health Sciences Facility II, Room 629
>>> University of Maryland, Baltimore
>>> 20 Penn St.
>>> Baltimore, MD 21201
>>>
>>> jalem...@outerbanks.umaryland.edu | (410) 706-7441
>>> http://mackerell.umaryland.edu/~jalemkul
>>>
>>> ==
>>> --
>>> Gromacs Users mailing list
>>>
>>> * Please search the archive at http://www.gromacs.org/Support
>>> /Mailing_Lists/GMX-Users_List before posting!
>>>
>>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>>
>>> * For (un)subscribe requests visit
>>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
>>> send a mail to gmx-users-requ...@gromacs.org.
>>>
>>>
> --
> ==
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 629
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> jalem...@outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
> ==
> --
> Gromacs Users mailing list
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> * Please search the archive at http://www.gromacs.org/Support
> /Mailing_Lists/GMX-Users_List before posting!
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Re: [gmx-users] PMF and lack if NPT equilibration

[Justin Lemkul]

On 10/10/16 4:57 AM, Alex wrote:

Thanks for your response.

My question is not in the sampling step as I have already pulled away two
parts and even picked out the configuration of each windows. But my
question is about simulation in each individual windows toward WHAM.

You means in the step six of the tutorial no necessarily need to do any NVT
or NPT before production simulation?



It's no different from any simulation.  You need to equilibrate under the 
ensemble you're going to use for data collection before you actually do that 
data collection.  If you would normally want NPT for a Gibbs free energy and 
can't get it for whatever reason (like the algorithmic limitation mentioned), 
then equilibrate with NPT to arrive at the desired density, and continue with 
NVT.  You won't get a Gibbs free energy, you'll get the Helmholtz free energy, 
but at least the density will be right.  Otherwise, build a bigger system that 
removes the restrictions of direction_periodic and use NPT.


-Justin


Thanks,
Alex


On Mon, Oct 10, 2016 at 2:17 AM, Justin Lemkul  wrote:




On 10/8/16 2:46 PM, Alex wrote:


Dear gromacs user,

In a PMF simulation of a short peptide on solid surface, I am using the
"direction-periodic" as "pull-coord1-geometry" in the Z  direction, then
as
you know the equilibration of the system in NPT ensemble is not doable for
the individual windows. So, for each windows of umbrella sampling, I am
going to do minimization and NVT equilibration and then MD production. I
was wondering if the lack of the NPT  equilibration would not badly affect
on the result PMF? If so, how can I compensate it somehow?



All you're doing is sampling under a different ensemble.  There's no
reason to think that a PMF requires an NPT ensemble.

-Justin

By the way, I nicely minimized. equilibrated (both NVT and NPT) and a 60 ns

of production simulation of my initial system before coming to the pulling
step.

Thanks.

Regards,
Alex



--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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Re: [gmx-users] PMF and lack if NPT equilibration

[Alex]

Thanks for your response.

My question is not in the sampling step as I have already pulled away two
parts and even picked out the configuration of each windows. But my
question is about simulation in each individual windows toward WHAM.

You means in the step six of the tutorial no necessarily need to do any NVT
or NPT before production simulation?

Thanks,
Alex


On Mon, Oct 10, 2016 at 2:17 AM, Justin Lemkul  wrote:

>
>
> On 10/8/16 2:46 PM, Alex wrote:
>
>> Dear gromacs user,
>>
>> In a PMF simulation of a short peptide on solid surface, I am using the
>> "direction-periodic" as "pull-coord1-geometry" in the Z  direction, then
>> as
>> you know the equilibration of the system in NPT ensemble is not doable for
>> the individual windows. So, for each windows of umbrella sampling, I am
>> going to do minimization and NVT equilibration and then MD production. I
>> was wondering if the lack of the NPT  equilibration would not badly affect
>> on the result PMF? If so, how can I compensate it somehow?
>>
>>
> All you're doing is sampling under a different ensemble.  There's no
> reason to think that a PMF requires an NPT ensemble.
>
> -Justin
>
> By the way, I nicely minimized. equilibrated (both NVT and NPT) and a 60 ns
>> of production simulation of my initial system before coming to the pulling
>> step.
>>
>> Thanks.
>>
>> Regards,
>> Alex
>>
>>
> --
> ==
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 629
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> jalem...@outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
> ==
> --
> Gromacs Users mailing list
>
> * Please search the archive at http://www.gromacs.org/Support
> /Mailing_Lists/GMX-Users_List before posting!
>
> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>
> * For (un)subscribe requests visit
> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
> send a mail to gmx-users-requ...@gromacs.org.
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Re: [gmx-users] PMF and lack if NPT equilibration

[Justin Lemkul]

On 10/8/16 2:46 PM, Alex wrote:

Dear gromacs user,

In a PMF simulation of a short peptide on solid surface, I am using the
"direction-periodic" as "pull-coord1-geometry" in the Z  direction, then as
you know the equilibration of the system in NPT ensemble is not doable for
the individual windows. So, for each windows of umbrella sampling, I am
going to do minimization and NVT equilibration and then MD production. I
was wondering if the lack of the NPT  equilibration would not badly affect
on the result PMF? If so, how can I compensate it somehow?



All you're doing is sampling under a different ensemble.  There's no reason to 
think that a PMF requires an NPT ensemble.


-Justin


By the way, I nicely minimized. equilibrated (both NVT and NPT) and a 60 ns
of production simulation of my initial system before coming to the pulling
step.

Thanks.

Regards,
Alex



--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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[gmx-users] PMF and lack if NPT equilibration

[Alex]

Dear gromacs user,

In a PMF simulation of a short peptide on solid surface, I am using the
"direction-periodic" as "pull-coord1-geometry" in the Z  direction, then as
you know the equilibration of the system in NPT ensemble is not doable for
the individual windows. So, for each windows of umbrella sampling, I am
going to do minimization and NVT equilibration and then MD production. I
was wondering if the lack of the NPT  equilibration would not badly affect
on the result PMF? If so, how can I compensate it somehow?

By the way, I nicely minimized. equilibrated (both NVT and NPT) and a 60 ns
of production simulation of my initial system before coming to the pulling
step.

Thanks.

Regards,
Alex
-- 
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[gmx-users] PMF of a short peptide on a solid surface

[Alexander Alexander]

Dear gromacs user,

In order to simulate the PMF of a adsorbed short peptide on a solid
surface, first I minimised and equlibrated(NVT and NPT) the system and then
I did a 60 ns of production run in which the peptide fully adsorbed to the
surface. I used these out put to pull away the peptide from the surface
using below mdp file (to produced required trajectory for generating
configuration):
+++
title= C16-Slab-Water-Na
integrator   = md
dt= 0.001 ; 1 fs
nsteps= 1000   ; 10 ns
xtc-precision  = 2000

nstenergy= 5000
nstlog   = 5000
nstxout-compressed   = 1000
nstxout  = 1000
nstlist  = 40

continuation = yes
gen-vel  = no
;gen-temp = 298.15
;gen-seed = 173529

constraint-algorithm = lincs
constraints  = h-bonds

cutoff-scheme= Verlet

coulombtype  = PME
rcoulomb = 1.3
vdwtype  = Cut-off
rvdw = 1.3
DispCorr = EnerPres

tcoupl   = Nose-Hoover  ;v-rescale  ;berendsen
tc-grps  = Protein Non-Protein
tau-t= 1.61 1.61
ref-t= 298.15  298.15
nhchainlength= 1
pbc  = xyz

pcoupl   = no
energygrps= Protein Slab Water_and_ions

pull = yes
pull-ngroups = 2
pull-ncoords = 1
pull-group1-name = Protein
pull-group2-name = Slab

pull-coord1-groups   = 1 2
pull-coord1-type = umbrella
pull-coord1-dim  = N N Y
pull-coord1-start= yes
pull-coord1-rate = 0.001  ;;;0.007
pull-coord1-vec  = 0.0 0.0 1.0
pull-coord1-geometry = direction-periodic
pull-coord1-k= 500   ;;;1000
pull-print-components= Yes


Although I do not use hard spring (500 and 1000) and fast pulling
rate(0.001 and 0.007) but I do not know why the peptide suddenly pulled
away from the slab in the second or third frame?

Thanks.
Alex
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Re: [gmx-users] PMF steadily increasing

[Christopher Neale]

Good that they are not interacting at large restraint distances. If they have 
opposite net charges, then one expects some attraction at any displacement, no 
matter how large. Obviously this attraction should decay into the noise at some 
distance, but I don't know how far that is and it should depend on salt 
concentration and also for your system the distribution of charges. For 
instance, if the nearest ends of the peptide and protein are 2 nm apart and 
have opposite net charge it would not surprise me at all if there was some 
attraction. If you can convince yourself that this is what is going on I 
presume that you could do some type of fit and extrapolation of the PMF that 
you do have.

I am worried about your comment that you are selecting frames. If you mean to 
start the run, then fine, but if you're scripting the selection of distances 
(frames) to use as wham input, then you've gone down the wrong track. My point 
about wham is that if you tell your wham program that the umbrella is centered 
at 6.0 nm but it is really centered at 6.05 nm then your going to get the wrong 
PMF and if there is any systematic bias between real center and what you tell 
wham then you would get a slope to your PMF.

I suggest that you do some test runs with (a) two LJ spheres and (b) with a 
Na-Cl pair. The first will help to confirm that you have no other error in your 
method and the second will give you a feel for separation distances at which 
the PMF flattens (and for your macromolecule analogy then you have to think in 
terms of the locations of point charges, not make the analogy to the center of 
mass).


From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se 
<gromacs.org_gmx-users-boun...@maillist.sys.kth.se> on behalf of Lukas 
Zimmermann <luk.zi...@gmail.com>
Sent: 20 June 2016 06:03:51
To: gmx-us...@gromacs.org
Subject: Re: [gmx-users] PMF steadily increasing

Thank you again for your remarks. This is what I found so far:

(1) With gmx mindist it was very clear that protein and peptide do not
interact. For the last 5 or 6 Umbrella Windows, the minimal distance
between the Pull groups was at least 2 nm
(2) That is indeed the case. The protein has net charge  -1 and the peptide
has charge +3.  Can you tell me what effect this might have?  I am unaware
that this might cause problems.
(3) I tried this, but this showed no apparent effect on the shape of the
curve.
(4) I do not understand in how far WHAM cares about the COM-COM distances.
I extract my frames from pull.xtc and I do not see each COM-COM distance
that would be required to have exactly, say, 0.1 nm
spacing, so I use a script which selects frames which resemble 0.1 nm
spacing as closely as possible, so there might some deviation.



2016-06-16 21:24 GMT+02:00 Lukas Zimmermann <luk.zi...@gmail.com>:

> Thank you very much for your suggestions. I will check your individual
> remarks and provide feedback.
>
> 2016-06-15 19:01 GMT+02:00 Christopher Neale <chris.ne...@alum.utoronto.ca
> >:
>
>> (1) Are the protein and peptide really never interacting at d=7 nm? I
>> presume you've got a peptide that would be maybe 5 nm long when fully
>> extended, and your dG minimum is at 1.5 nm, so giving half the peptide
>> length that would imply possible contact at 4 nm, so I expect 7 nm is
>> sufficient, but gmx mindist can tell you for certain. For example, if the
>> protein forms an overhanging pocket around the binding site, then it is
>> quite possible that an unfolded peptide would be sometimes (even rarely)
>> contacting a 568 residue protein even at a COM-COM distance of 7 nm.
>>
>> (2) net charge positive on one and negative on the other?
>>
>> (3) unconverged? Did you try eliminating the first half of your
>> production sampling and see if this fixes the issue?
>>
>> (4) did you do wham properly? Your mdp file indicate that your windows
>> are not *exactly* at 0.1 and 0.2 nm increments (use of
>> pull_coord1_start=yes), which is fine but only as long as wham doesn't
>> think your windows are exactly at these increments.
>>
>> There may be some entropy change as the peptide becomes unbound and can
>> then sample full X and Y, but on its own that should not continue to impact
>> the sampling after contact is permanently broken.
>> 
>> From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se <
>> gromacs.org_gmx-users-boun...@maillist.sys.kth.se> on behalf of Lukas
>> Zimmermann <luk.zi...@gmail.com>
>> Sent: 15 June 2016 12:45:51
>> To: gmx-us...@gromacs.org
>> Subject: [gmx-users] PMF steadily increasing
>>
>> Dear GROMACS community,
>>
>> I performed umbrella sampling study to estimate the binding free energy
>> betw

Re: [gmx-users] PMF steadily increasing

[Lukas Zimmermann]

Thank you again for your remarks. This is what I found so far:

(1) With gmx mindist it was very clear that protein and peptide do not
interact. For the last 5 or 6 Umbrella Windows, the minimal distance
between the Pull groups was at least 2 nm
(2) That is indeed the case. The protein has net charge  -1 and the peptide
has charge +3.  Can you tell me what effect this might have?  I am unaware
that this might cause problems.
(3) I tried this, but this showed no apparent effect on the shape of the
curve.
(4) I do not understand in how far WHAM cares about the COM-COM distances.
I extract my frames from pull.xtc and I do not see each COM-COM distance
that would be required to have exactly, say, 0.1 nm
spacing, so I use a script which selects frames which resemble 0.1 nm
spacing as closely as possible, so there might some deviation.



2016-06-16 21:24 GMT+02:00 Lukas Zimmermann <luk.zi...@gmail.com>:

> Thank you very much for your suggestions. I will check your individual
> remarks and provide feedback.
>
> 2016-06-15 19:01 GMT+02:00 Christopher Neale <chris.ne...@alum.utoronto.ca
> >:
>
>> (1) Are the protein and peptide really never interacting at d=7 nm? I
>> presume you've got a peptide that would be maybe 5 nm long when fully
>> extended, and your dG minimum is at 1.5 nm, so giving half the peptide
>> length that would imply possible contact at 4 nm, so I expect 7 nm is
>> sufficient, but gmx mindist can tell you for certain. For example, if the
>> protein forms an overhanging pocket around the binding site, then it is
>> quite possible that an unfolded peptide would be sometimes (even rarely)
>> contacting a 568 residue protein even at a COM-COM distance of 7 nm.
>>
>> (2) net charge positive on one and negative on the other?
>>
>> (3) unconverged? Did you try eliminating the first half of your
>> production sampling and see if this fixes the issue?
>>
>> (4) did you do wham properly? Your mdp file indicate that your windows
>> are not *exactly* at 0.1 and 0.2 nm increments (use of
>> pull_coord1_start=yes), which is fine but only as long as wham doesn't
>> think your windows are exactly at these increments.
>>
>> There may be some entropy change as the peptide becomes unbound and can
>> then sample full X and Y, but on its own that should not continue to impact
>> the sampling after contact is permanently broken.
>> 
>> From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se <
>> gromacs.org_gmx-users-boun...@maillist.sys.kth.se> on behalf of Lukas
>> Zimmermann <luk.zi...@gmail.com>
>> Sent: 15 June 2016 12:45:51
>> To: gmx-us...@gromacs.org
>> Subject: [gmx-users] PMF steadily increasing
>>
>> Dear GROMACS community,
>>
>> I performed umbrella sampling study to estimate the binding free energy
>> between a globular
>> protein with 568 residues and a small peptide with 13 residues. I use the
>> pull code with k = 800 and rate = 0.005 to generate the initial
>> conformations over the time course of 1200 ps. The
>> center of masses distance between the pull groups ranges from  1.4 nm ad
>> 7.8 nm in the pull trajectory.
>>
>> I then extract conformations from pull.xtc with a spacing of 0.1 nm until
>> 3
>> nm distance
>> and a spacing of 0.2 nm for the remainder, yielding 38 windows in total.
>> After having
>> equilibrated each window with NVT and NPT under full position restraints,
>> I
>> conducted
>> production simulation under NPT ensemble for 14 ns for each window.
>> Finally, gmx wham
>> computed the PMF curve which you can see here:
>>
>> https://www.dropbox.com/s/fp7ol41qoyokmjm/profile.xvg?dl=0
>>
>> and this is the associated histogram:
>>
>> https://www.dropbox.com/s/bp6obymjc2qeu37/histo.xvg?dl=0
>>
>> Please find here my MDP pull parameters:
>>
>> pull= yes
>> pull_ngroups= 2
>> pull_ncoords= 1
>> pull_group1_name= chainB; Protein
>> pull_group2_name= chainC; Peptide
>> pull_coord1_type= umbrella
>> pull_coord1_geometry= distance
>> pull_coord1_groups  = 1 2
>> pull_coord1_dim = N N Y
>> pull_coord1_rate= 0.0
>> pull_coord1_k   = 800
>> pull_coord1_start   = yes
>>
>>
>> I would now be very interested why the curve does not become flat beyond
>> some certain distance, but rather seems to increase in a linear fashion,
>> though the distance between the pull groups is sufficiently large. Could
>> this be related to entropic effects? Is th

Re: [gmx-users] PMF steadily increasing

[Lukas Zimmermann]

Thank you very much for your suggestions. I will check your individual
remarks and provide feedback.

2016-06-15 19:01 GMT+02:00 Christopher Neale <chris.ne...@alum.utoronto.ca>:

> (1) Are the protein and peptide really never interacting at d=7 nm? I
> presume you've got a peptide that would be maybe 5 nm long when fully
> extended, and your dG minimum is at 1.5 nm, so giving half the peptide
> length that would imply possible contact at 4 nm, so I expect 7 nm is
> sufficient, but gmx mindist can tell you for certain. For example, if the
> protein forms an overhanging pocket around the binding site, then it is
> quite possible that an unfolded peptide would be sometimes (even rarely)
> contacting a 568 residue protein even at a COM-COM distance of 7 nm.
>
> (2) net charge positive on one and negative on the other?
>
> (3) unconverged? Did you try eliminating the first half of your production
> sampling and see if this fixes the issue?
>
> (4) did you do wham properly? Your mdp file indicate that your windows are
> not *exactly* at 0.1 and 0.2 nm increments (use of pull_coord1_start=yes),
> which is fine but only as long as wham doesn't think your windows are
> exactly at these increments.
>
> There may be some entropy change as the peptide becomes unbound and can
> then sample full X and Y, but on its own that should not continue to impact
> the sampling after contact is permanently broken.
> 
> From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se <
> gromacs.org_gmx-users-boun...@maillist.sys.kth.se> on behalf of Lukas
> Zimmermann <luk.zi...@gmail.com>
> Sent: 15 June 2016 12:45:51
> To: gmx-us...@gromacs.org
> Subject: [gmx-users] PMF steadily increasing
>
> Dear GROMACS community,
>
> I performed umbrella sampling study to estimate the binding free energy
> between a globular
> protein with 568 residues and a small peptide with 13 residues. I use the
> pull code with k = 800 and rate = 0.005 to generate the initial
> conformations over the time course of 1200 ps. The
> center of masses distance between the pull groups ranges from  1.4 nm ad
> 7.8 nm in the pull trajectory.
>
> I then extract conformations from pull.xtc with a spacing of 0.1 nm until 3
> nm distance
> and a spacing of 0.2 nm for the remainder, yielding 38 windows in total.
> After having
> equilibrated each window with NVT and NPT under full position restraints, I
> conducted
> production simulation under NPT ensemble for 14 ns for each window.
> Finally, gmx wham
> computed the PMF curve which you can see here:
>
> https://www.dropbox.com/s/fp7ol41qoyokmjm/profile.xvg?dl=0
>
> and this is the associated histogram:
>
> https://www.dropbox.com/s/bp6obymjc2qeu37/histo.xvg?dl=0
>
> Please find here my MDP pull parameters:
>
> pull= yes
> pull_ngroups= 2
> pull_ncoords= 1
> pull_group1_name= chainB; Protein
> pull_group2_name= chainC; Peptide
> pull_coord1_type= umbrella
> pull_coord1_geometry= distance
> pull_coord1_groups  = 1 2
> pull_coord1_dim = N N Y
> pull_coord1_rate= 0.0
> pull_coord1_k   = 800
> pull_coord1_start   = yes
>
>
> I would now be very interested why the curve does not become flat beyond
> some certain distance, but rather seems to increase in a linear fashion,
> though the distance between the pull groups is sufficiently large. Could
> this be related to entropic effects? Is there a way to
> have the PMF properly normalized?
>
> The force field here is GROMOS 53a6 with SPC water. Temperature is coupled
> to
> 310 K and pressure to 1 bar.  Cutoffs are 1.4 nm, longe range ES are
> resolved with PME
> and DispCorr is set to EnerPress. Bonds are constrained with LINCS.
>
> The Protein is prevented from rotation by having three CA atoms restrained
> with FC 1000.
>
>
> Thank you very much, I appreciate any help and suggestions.
>
> Lukas
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> Gromacs Users mailing list
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Re: [gmx-users] PMF steadily increasing

[Christopher Neale]

(1) Are the protein and peptide really never interacting at d=7 nm? I presume 
you've got a peptide that would be maybe 5 nm long when fully extended, and 
your dG minimum is at 1.5 nm, so giving half the peptide length that would 
imply possible contact at 4 nm, so I expect 7 nm is sufficient, but gmx mindist 
can tell you for certain. For example, if the protein forms an overhanging 
pocket around the binding site, then it is quite possible that an unfolded 
peptide would be sometimes (even rarely) contacting a 568 residue protein even 
at a COM-COM distance of 7 nm.

(2) net charge positive on one and negative on the other?

(3) unconverged? Did you try eliminating the first half of your production 
sampling and see if this fixes the issue?

(4) did you do wham properly? Your mdp file indicate that your windows are not 
*exactly* at 0.1 and 0.2 nm increments (use of pull_coord1_start=yes), which is 
fine but only as long as wham doesn't think your windows are exactly at these 
increments.

There may be some entropy change as the peptide becomes unbound and can then 
sample full X and Y, but on its own that should not continue to impact the 
sampling after contact is permanently broken.

From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se 
<gromacs.org_gmx-users-boun...@maillist.sys.kth.se> on behalf of Lukas 
Zimmermann <luk.zi...@gmail.com>
Sent: 15 June 2016 12:45:51
To: gmx-us...@gromacs.org
Subject: [gmx-users] PMF steadily increasing

Dear GROMACS community,

I performed umbrella sampling study to estimate the binding free energy
between a globular
protein with 568 residues and a small peptide with 13 residues. I use the
pull code with k = 800 and rate = 0.005 to generate the initial
conformations over the time course of 1200 ps. The
center of masses distance between the pull groups ranges from  1.4 nm ad
7.8 nm in the pull trajectory.

I then extract conformations from pull.xtc with a spacing of 0.1 nm until 3
nm distance
and a spacing of 0.2 nm for the remainder, yielding 38 windows in total.
After having
equilibrated each window with NVT and NPT under full position restraints, I
conducted
production simulation under NPT ensemble for 14 ns for each window.
Finally, gmx wham
computed the PMF curve which you can see here:

https://www.dropbox.com/s/fp7ol41qoyokmjm/profile.xvg?dl=0

and this is the associated histogram:

https://www.dropbox.com/s/bp6obymjc2qeu37/histo.xvg?dl=0

Please find here my MDP pull parameters:

pull= yes
pull_ngroups= 2
pull_ncoords= 1
pull_group1_name= chainB; Protein
pull_group2_name= chainC; Peptide
pull_coord1_type= umbrella
pull_coord1_geometry= distance
pull_coord1_groups  = 1 2
pull_coord1_dim = N N Y
pull_coord1_rate= 0.0
pull_coord1_k   = 800
pull_coord1_start   = yes


I would now be very interested why the curve does not become flat beyond
some certain distance, but rather seems to increase in a linear fashion,
though the distance between the pull groups is sufficiently large. Could
this be related to entropic effects? Is there a way to
have the PMF properly normalized?

The force field here is GROMOS 53a6 with SPC water. Temperature is coupled
to
310 K and pressure to 1 bar.  Cutoffs are 1.4 nm, longe range ES are
resolved with PME
and DispCorr is set to EnerPress. Bonds are constrained with LINCS.

The Protein is prevented from rotation by having three CA atoms restrained
with FC 1000.


Thank you very much, I appreciate any help and suggestions.

Lukas
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[gmx-users] PMF steadily increasing

[Lukas Zimmermann]

Dear GROMACS community,

I performed umbrella sampling study to estimate the binding free energy
between a globular
protein with 568 residues and a small peptide with 13 residues. I use the
pull code with k = 800 and rate = 0.005 to generate the initial
conformations over the time course of 1200 ps. The
center of masses distance between the pull groups ranges from  1.4 nm ad
7.8 nm in the pull trajectory.

I then extract conformations from pull.xtc with a spacing of 0.1 nm until 3
nm distance
and a spacing of 0.2 nm for the remainder, yielding 38 windows in total.
After having
equilibrated each window with NVT and NPT under full position restraints, I
conducted
production simulation under NPT ensemble for 14 ns for each window.
Finally, gmx wham
computed the PMF curve which you can see here:

https://www.dropbox.com/s/fp7ol41qoyokmjm/profile.xvg?dl=0

and this is the associated histogram:

https://www.dropbox.com/s/bp6obymjc2qeu37/histo.xvg?dl=0

Please find here my MDP pull parameters:

pull= yes
pull_ngroups= 2
pull_ncoords= 1
pull_group1_name= chainB; Protein
pull_group2_name= chainC; Peptide
pull_coord1_type= umbrella
pull_coord1_geometry= distance
pull_coord1_groups  = 1 2
pull_coord1_dim = N N Y
pull_coord1_rate= 0.0
pull_coord1_k   = 800
pull_coord1_start   = yes


I would now be very interested why the curve does not become flat beyond
some certain distance, but rather seems to increase in a linear fashion,
though the distance between the pull groups is sufficiently large. Could
this be related to entropic effects? Is there a way to
have the PMF properly normalized?

The force field here is GROMOS 53a6 with SPC water. Temperature is coupled
to
310 K and pressure to 1 bar.  Cutoffs are 1.4 nm, longe range ES are
resolved with PME
and DispCorr is set to EnerPress. Bonds are constrained with LINCS.

The Protein is prevented from rotation by having three CA atoms restrained
with FC 1000.


Thank you very much, I appreciate any help and suggestions.

Lukas
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[gmx-users] PMF of a single water molecule respect to a surface

[Alexander Alexander]

Dear Gromacs user,

I am calculation the PMF of a single water molecule to pull it away from
top of metallic surface along vacuum in the Z direction ,following the
Justin umbrella tutorial. I am only  interested in the behavior of PMF in
0.002 nm to 0.8 nm intervalon top of the surface, but I do not why the
population of the generated frames in this interval is really low and then
the result is so poor.

So, would you please let me know which parameter I should play around with?

I just tried 0.001 instead 0.01 as the "pull_coord1_rate" and simultaneously
3500 instead of 1000 as "pull_coord1_k", but the result got even worse.

Best regards,

Alex
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Re: [gmx-users] PMF of a single water molecule respect to a surface

[Justin Lemkul]

On 2/12/16 8:47 AM, Alexander Alexander wrote:

Dear Gromacs user,

I am calculation the PMF of a single water molecule to pull it away from
top of metallic surface along vacuum in the Z direction ,following the
Justin umbrella tutorial. I am only  interested in the behavior of PMF in
0.002 nm to 0.8 nm intervalon top of the surface, but I do not why the
population of the generated frames in this interval is really low and then
the result is so poor.

So, would you please let me know which parameter I should play around with?

I just tried 0.001 instead 0.01 as the "pull_coord1_rate" and simultaneously
3500 instead of 1000 as "pull_coord1_k", but the result got even worse.



How often are you saving the snapshots?  I presume you're referring to the 
generation of initial coordinates as references for the individual windows. If 
you don't save frequently enough, you may miss one that you need, although it 
should be pretty easy to capture something "close enough" to start.


Your biggest problem is the very short distance you're considering here.  0.002 
nm?  You're going to have massive repulsion at that distance, such that you're 
not likely to observe any stable configurations there.  Probably anything less 
than 0.1 or 0.2 nm is going to be pretty unstable, depending on the nature of 
the interactions.


-Justin

--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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[gmx-users] pmf-gwham

[Rasha Alqus]

Dear All,



I am doing umbrella sample for a system and I have a question. on my system I  
have extra two angle_restraints_z on the pulled group, and one position 
restrain on the reference group.  Dose g-wham accept having this number of 
restrains on the system. Dose having many restrains effect my calculation.



Thank you so much I advance for the help



R.A
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Re: [gmx-users] PMF calculation_ Constraint

[Sepideh Kavousi]

Dear Justin.
Thanks for response. I used constraint method because I wanted to calculate
MSD, How does using a bigger box helps me? because when  I make box bigger,
I need to run a little bit to equilibrate system, and again the tocopherol
can move and come out of the box.

On Tue, Sep 22, 2015 at 5:45 PM, Justin Lemkul  wrote:

>
>
> On 9/22/15 3:46 PM, Sepideh Kavousi wrote:
>
>> Dear Gromacs users
>>
>> I want to calculate the PMF of tocopherol in DMPC bilayer system. For this
>> means, I used Constraint method. the pull code in my .mdp file is :
>>
>> pull = constraint
>> pull-geometry = distance;distance, direction, or cylinder
>> pull-dim = N N Y
>> pull-constr-tol = 1e-6
>> pull-start = yes;add current COM distance to
>> pull_init?
>> pull-print-reference = no
>> pull-nstxout = 1
>> pull-nstfout = 5
>> pull-ngroups = 2
>> pull-ncoords = 1
>> pull-group1-name = DMPC
>> pull-group2-name = VIT
>> pull-coord1-groups = 1 2
>> pull-coord1-init = 0.0
>>
>>
>> In my output file which shows force over time, we have some sudden
>> diverges
>> of force to a very high number.
>> I realized it is because of the boundary condition, one part of molecule
>> comes out of the box and enters from the other side of the box and it
>> needs
>> a huge force to keep the molecule at the same position. Can you please
>> help
>> me how to solve this problem
>>
>>
> Use a bigger box, use a shorter reaction coordinate, or use an umbrella
> sampling method that supports PBC.  I suspect any output using the
> constraint method will be very poorly converged.
>
> -Justin
>
> --
> ==
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 629
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> jalem...@outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
> ==
> --
> Gromacs Users mailing list
>
> * Please search the archive at
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> posting!
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[gmx-users] PMF calculation_ Constraint

[Sepideh Kavousi]

Dear Gromacs users

I want to calculate the PMF of tocopherol in DMPC bilayer system. For this
means, I used Constraint method. the pull code in my .mdp file is :

pull = constraint
pull-geometry = distance;distance, direction, or cylinder
pull-dim = N N Y
pull-constr-tol = 1e-6
pull-start = yes;add current COM distance to pull_init?
pull-print-reference = no
pull-nstxout = 1
pull-nstfout = 5
pull-ngroups = 2
pull-ncoords = 1
pull-group1-name = DMPC
pull-group2-name = VIT
pull-coord1-groups = 1 2
pull-coord1-init = 0.0


In my output file which shows force over time, we have some sudden diverges
of force to a very high number.
I realized it is because of the boundary condition, one part of molecule
comes out of the box and enters from the other side of the box and it needs
a huge force to keep the molecule at the same position. Can you please help
me how to solve this problem
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Re: [gmx-users] PMF calculation_ Constraint

[Justin Lemkul]

On 9/22/15 3:46 PM, Sepideh Kavousi wrote:

Dear Gromacs users

I want to calculate the PMF of tocopherol in DMPC bilayer system. For this
means, I used Constraint method. the pull code in my .mdp file is :

pull = constraint
pull-geometry = distance;distance, direction, or cylinder
pull-dim = N N Y
pull-constr-tol = 1e-6
pull-start = yes;add current COM distance to pull_init?
pull-print-reference = no
pull-nstxout = 1
pull-nstfout = 5
pull-ngroups = 2
pull-ncoords = 1
pull-group1-name = DMPC
pull-group2-name = VIT
pull-coord1-groups = 1 2
pull-coord1-init = 0.0


In my output file which shows force over time, we have some sudden diverges
of force to a very high number.
I realized it is because of the boundary condition, one part of molecule
comes out of the box and enters from the other side of the box and it needs
a huge force to keep the molecule at the same position. Can you please help
me how to solve this problem



Use a bigger box, use a shorter reaction coordinate, or use an umbrella sampling 
method that supports PBC.  I suspect any output using the constraint method will 
be very poorly converged.


-Justin

--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0

[Eudes Fileti]

Dear Chris, thanks for the help.
Yes, I set the temperature properly.

Also I checked the line that you mentioned and it is exactly the same in my
version of gromacs (5.0.4).

I have not yet tried using another tool wham. I'll search the web and if I
find something, I report shortly.

eef



 Dear Eudes: then I return to being stumped. It sure looks like it might
be an issue with a constant

 somewhere. I'll note that v5.0.5 g_wham uses what I think is an incorrect
constant to convert to kcal
 (http://redmine.gromacs.org/issues/1787), but you're using kj so that
shouldn't be it. The gas constant
 defined by g_wham on line 1086 in v5.0.5 is also a little bit different
from the one used in core gromacs
 (for e.g. replica exchange to get the boltzmann constant), though again I
don't see how this could do
 anything but affect the overall scale by a tiny amount. However, I do
wonder about 8.314e-3 in lines like
 this where it possibly could affect
 the value: denom +=
invg*window[j].N[k]*exp(-U/(8.314e-3*opt-Temperature) + window[j].z[k]);
(line 966
 in calc_profile() in v5.0.5) Are you using g_wham? Can you try a
different wham software and see if you
 get the same thing? Also, are you setting -temp properly in g_wham ?
Beyond that, I've run out of ideas.
 If you do ever sort this out, I'd appreciate it if you could send me an
email off list to let me know (and post
 it here of course, I just don't always check the list).
 Thank you, Chris.


___
Eudes Eterno Fileti
Instituto de Ciência e Tecnologia da UNIFESP
Rua Talim, 330, São José dos Campos - SP
Página: sites.google.com/site/fileti/

On 28 July 2015 at 08:59, Eudes Fileti fil...@gmail.com wrote:

 Dear Chris, thank you for help. I performed the test you suggested, with
 no pressure coupling. Note that the behavior of the profile remained the
 same even with no pressure coupling.
 https://goo.gl/photos/2d8tsYFwp2eHCuCWA

 The simulation parameters were exactly the same (except the sampling in
 the test was 5 ns window and by coupling pressure, which was turned off).

 Bests
 eef

 ___
 Eudes Eterno Fileti
 Instituto de Ciência e Tecnologia da UNIFESP
 Rua Talim, 330, São José dos Campos - SP
 Página: sites.google.com/site/fileti/


 --

 Message: 2
 Date: Sun, 26 Jul 2015 02:45:50 +
 From: Christopher Neale chris.ne...@alum.utoronto.ca
 To: gmx-us...@gromacs.org gmx-us...@gromacs.org
 Subject: Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0
 (Eudes  Fileti)
 Message-ID:
 
 blupr03mb184037e6ef2ec6d63bebe21c5...@blupr03mb184.namprd03.prod.outlook.com
 

 Content-Type: text/plain; charset=iso-8859-1

 Dear Eudes:

 Glad that you solved one of the two issues. As for the bumps in the PMF,
 I have a new theory: the bumps come from pressure coupling. When the
 sampled distance, d, between the two molecules fluctuate a little closer
 than the center of restraint, d0, that adds a repulsive force that
 contributes to the virial and the box gets a little larger. Conversely,
 slight fluctuations of d that are larger than d0 will add a small bias to
 box contraction. This should be more noticeable when the restrained
 distance involves larger masses.

 It is at the moment unclear to me whether this might exert an effect
 indirectly due to overall system density or more directly as coordinate
 scaling impacts the instantaneous value of d. If it is the latter, then
 semi-isotropic pressure coupling, may also enhance the effect since the
 virial will be computed independently along the order parameter (I presume)
 and hence there is less noise from other dimensions.

 Can you please try again without pressure coupling (single precision
 should be fine for this test). Hopefully this is not the source of the
 bumps because, if it is affecting the PMF noticeably and the underlying
 free energy surface has a large gradient, then d will always be on one side
 of d0 and the effect will not be merely bumps but also some type of bias in
 the PMF. Whether this bias is accurate or artifactual falls outside of my
 mathematical abilities. The thing is, the force is a real force between
 real atoms so it seems like it really should be included in the virial (as
 it certainly is... I checked). I can tell you one thing for sure: the
 effect on box volume is real and noticeable. That is, if you look at the
 average system volume when dd0, it differs in a statistically significant
 manner from the average system volume when dd0 (something that I also
 checked).

 Thank you for looking into this further,
 Chris.

 
 From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se 
 gromacs.org_gmx-users-boun...@maillist.sys.kth.se on behalf of Eudes
 Fileti fil...@gmail.com
 Sent: 24 July 2015 16:47
 To: gromacs.org_gmx-users@maillist.sys.kth.se
 Subject: Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0
 (Eudes

Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0

[Jochen Hub]

Hi Eudes,

do you have one bump per umbrella histogram? If so, this typically means
that your histograms do not have the right width. Does our temperature
specified in the g_wham options not correspond to temperature in your
mdp files?

Otherwise, I am not sure. I would take very close look at the
histograms, is their width exactly what they should be ( sqrt(RT/f_c),
where R is the gas constant and f_c the umbrella force constant)?

Best,
Jochen

Am 28/07/15 um 13:59 schrieb Eudes Fileti:
 Dear Chris, thank you for help. I performed the test you suggested, with no
 pressure coupling. Note that the behavior of the profile remained the same
 even with no pressure coupling.
 https://goo.gl/photos/2d8tsYFwp2eHCuCWA
 
 The simulation parameters were exactly the same (except the sampling in the
 test was 5 ns window and by coupling pressure, which was turned off).
 
 Bests
 eef
 
 ___
 Eudes Eterno Fileti
 Instituto de Ciência e Tecnologia da UNIFESP
 Rua Talim, 330, São José dos Campos - SP
 Página: sites.google.com/site/fileti/
 
 
 --

 Message: 2
 Date: Sun, 26 Jul 2015 02:45:50 +
 From: Christopher Neale chris.ne...@alum.utoronto.ca
 To: gmx-us...@gromacs.org gmx-us...@gromacs.org
 Subject: Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0
 (Eudes  Fileti)
 Message-ID:
 
 blupr03mb184037e6ef2ec6d63bebe21c5...@blupr03mb184.namprd03.prod.outlook.com


 Content-Type: text/plain; charset=iso-8859-1

 Dear Eudes:

 Glad that you solved one of the two issues. As for the bumps in the PMF, I
 have a new theory: the bumps come from pressure coupling. When the sampled
 distance, d, between the two molecules fluctuate a little closer than the
 center of restraint, d0, that adds a repulsive force that contributes to
 the virial and the box gets a little larger. Conversely, slight
 fluctuations of d that are larger than d0 will add a small bias to box
 contraction. This should be more noticeable when the restrained distance
 involves larger masses.

 It is at the moment unclear to me whether this might exert an effect
 indirectly due to overall system density or more directly as coordinate
 scaling impacts the instantaneous value of d. If it is the latter, then
 semi-isotropic pressure coupling, may also enhance the effect since the
 virial will be computed independently along the order parameter (I presume)
 and hence there is less noise from other dimensions.

 Can you please try again without pressure coupling (single precision
 should be fine for this test). Hopefully this is not the source of the
 bumps because, if it is affecting the PMF noticeably and the underlying
 free energy surface has a large gradient, then d will always be on one side
 of d0 and the effect will not be merely bumps but also some type of bias in
 the PMF. Whether this bias is accurate or artifactual falls outside of my
 mathematical abilities. The thing is, the force is a real force between
 real atoms so it seems like it really should be included in the virial (as
 it certainly is... I checked). I can tell you one thing for sure: the
 effect on box volume is real and noticeable. That is, if you look at the
 average system volume when dd0, it differs in a statistically significant
 manner from the average system volume when dd0 (something that I also
 checked).

 Thank you for looking into this further,
 Chris.

 
 From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se 
 gromacs.org_gmx-users-boun...@maillist.sys.kth.se on behalf of Eudes
 Fileti fil...@gmail.com
 Sent: 24 July 2015 16:47
 To: gromacs.org_gmx-users@maillist.sys.kth.se
 Subject: Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0
 (Eudes Fileti)

 Hello Chris, I write to report the results of the tests you suggested.
 To recap, I have two problems to solve. 1) The bad sampling around z = 0
 and 2) the bumps along to the profile.

 I solved the first discarding all the my initial configurations and
 performing a new pulling (SMD). Only this time I used a higher force
 constant (5000 kJ/mol nm2). Thus I got configurations close to z = 0, where
 they were not generated.

 For the second problem, you suggested recalculate the PMF using double
 precision. The results of this test showed that it does not solve the
 problem, on the contrary the bumps were even more pronounced, as indicated
 by the plot in this link. https://goo.gl/photos/wGNhdyNG9pdqGfcB6

 All tests were performed with prototypes simulations, with 40 windows of 2
 ns spaced by 0.1 nm. A larger sample is obviously necessary for reliable
 profiles, but this was enough to show the trend that I wanted to watch.

 As I have mentioned before, I've done several tests aiming to eliminate
 these bumps: use of higher sampling, up to 20ns per window; reducing the
 spacing between the windows (from 0.1 to 0.05 nm); changing the spring
 constant from 1000 up to 5000 kJ/mol nm2, use

Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0

[Eudes Fileti]

Dear Chris, thank you for help. I performed the test you suggested, with no
pressure coupling. Note that the behavior of the profile remained the same
even with no pressure coupling.
https://goo.gl/photos/2d8tsYFwp2eHCuCWA

The simulation parameters were exactly the same (except the sampling in the
test was 5 ns window and by coupling pressure, which was turned off).

Bests
eef

___
Eudes Eterno Fileti
Instituto de Ciência e Tecnologia da UNIFESP
Rua Talim, 330, São José dos Campos - SP
Página: sites.google.com/site/fileti/


 --

 Message: 2
 Date: Sun, 26 Jul 2015 02:45:50 +
 From: Christopher Neale chris.ne...@alum.utoronto.ca
 To: gmx-us...@gromacs.org gmx-us...@gromacs.org
 Subject: Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0
 (Eudes  Fileti)
 Message-ID:
 
 blupr03mb184037e6ef2ec6d63bebe21c5...@blupr03mb184.namprd03.prod.outlook.com
 

 Content-Type: text/plain; charset=iso-8859-1

 Dear Eudes:

 Glad that you solved one of the two issues. As for the bumps in the PMF, I
 have a new theory: the bumps come from pressure coupling. When the sampled
 distance, d, between the two molecules fluctuate a little closer than the
 center of restraint, d0, that adds a repulsive force that contributes to
 the virial and the box gets a little larger. Conversely, slight
 fluctuations of d that are larger than d0 will add a small bias to box
 contraction. This should be more noticeable when the restrained distance
 involves larger masses.

 It is at the moment unclear to me whether this might exert an effect
 indirectly due to overall system density or more directly as coordinate
 scaling impacts the instantaneous value of d. If it is the latter, then
 semi-isotropic pressure coupling, may also enhance the effect since the
 virial will be computed independently along the order parameter (I presume)
 and hence there is less noise from other dimensions.

 Can you please try again without pressure coupling (single precision
 should be fine for this test). Hopefully this is not the source of the
 bumps because, if it is affecting the PMF noticeably and the underlying
 free energy surface has a large gradient, then d will always be on one side
 of d0 and the effect will not be merely bumps but also some type of bias in
 the PMF. Whether this bias is accurate or artifactual falls outside of my
 mathematical abilities. The thing is, the force is a real force between
 real atoms so it seems like it really should be included in the virial (as
 it certainly is... I checked). I can tell you one thing for sure: the
 effect on box volume is real and noticeable. That is, if you look at the
 average system volume when dd0, it differs in a statistically significant
 manner from the average system volume when dd0 (something that I also
 checked).

 Thank you for looking into this further,
 Chris.

 
 From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se 
 gromacs.org_gmx-users-boun...@maillist.sys.kth.se on behalf of Eudes
 Fileti fil...@gmail.com
 Sent: 24 July 2015 16:47
 To: gromacs.org_gmx-users@maillist.sys.kth.se
 Subject: Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0
 (Eudes Fileti)

 Hello Chris, I write to report the results of the tests you suggested.
 To recap, I have two problems to solve. 1) The bad sampling around z = 0
 and 2) the bumps along to the profile.

 I solved the first discarding all the my initial configurations and
 performing a new pulling (SMD). Only this time I used a higher force
 constant (5000 kJ/mol nm2). Thus I got configurations close to z = 0, where
 they were not generated.

 For the second problem, you suggested recalculate the PMF using double
 precision. The results of this test showed that it does not solve the
 problem, on the contrary the bumps were even more pronounced, as indicated
 by the plot in this link. https://goo.gl/photos/wGNhdyNG9pdqGfcB6

 All tests were performed with prototypes simulations, with 40 windows of 2
 ns spaced by 0.1 nm. A larger sample is obviously necessary for reliable
 profiles, but this was enough to show the trend that I wanted to watch.

 As I have mentioned before, I've done several tests aiming to eliminate
 these bumps: use of higher sampling, up to 20ns per window; reducing the
 spacing between the windows (from 0.1 to 0.05 nm); changing the spring
 constant from 1000 up to 5000 kJ/mol nm2, use of two different versions of
 the Gromacs (4.6 e 5.0) and also I tested it with two different sets of
 initial settings.

 None of this attempts solved the bumps problem.

 If you (or someone else) have any other tips please let me know.

 Thank you
 eef

 ___
 Eudes Eterno Fileti
 Instituto de Ci?ncia e Tecnologia da UNIFESP
 Rua Talim, 330, S?o Jos? dos Campos - SP
 P?gina: sites.google.com/site/fileti/

 
  --
 
  Message: 4
  Date: Wed, 22

Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0

[Eudes Fileti]

Dear Chris, thank you for help. I performed the test you suggested, with no
pressure coupling. Note that the behavior of the profile remained the same
even with no pressure coupling.
https://goo.gl/photos/2d8tsYFwp2eHCuCWA

The simulation parameters were exactly the same (except the sampling in the
test was 5 ns window and by coupling pressure, which was turned off).

Bests
eef

___
Eudes Eterno Fileti
Instituto de Ciência e Tecnologia da UNIFESP
Rua Talim, 330, São José dos Campos - SP
Página: sites.google.com/site/fileti/


 --

 Message: 2
 Date: Sun, 26 Jul 2015 02:45:50 +
 From: Christopher Neale chris.ne...@alum.utoronto.ca
 To: gmx-us...@gromacs.org gmx-us...@gromacs.org
 Subject: Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0
 (Eudes  Fileti)
 Message-ID:
 
 blupr03mb184037e6ef2ec6d63bebe21c5...@blupr03mb184.namprd03.prod.outlook.com
 

 Content-Type: text/plain; charset=iso-8859-1

 Dear Eudes:

 Glad that you solved one of the two issues. As for the bumps in the PMF, I
 have a new theory: the bumps come from pressure coupling. When the sampled
 distance, d, between the two molecules fluctuate a little closer than the
 center of restraint, d0, that adds a repulsive force that contributes to
 the virial and the box gets a little larger. Conversely, slight
 fluctuations of d that are larger than d0 will add a small bias to box
 contraction. This should be more noticeable when the restrained distance
 involves larger masses.

 It is at the moment unclear to me whether this might exert an effect
 indirectly due to overall system density or more directly as coordinate
 scaling impacts the instantaneous value of d. If it is the latter, then
 semi-isotropic pressure coupling, may also enhance the effect since the
 virial will be computed independently along the order parameter (I presume)
 and hence there is less noise from other dimensions.

 Can you please try again without pressure coupling (single precision
 should be fine for this test). Hopefully this is not the source of the
 bumps because, if it is affecting the PMF noticeably and the underlying
 free energy surface has a large gradient, then d will always be on one side
 of d0 and the effect will not be merely bumps but also some type of bias in
 the PMF. Whether this bias is accurate or artifactual falls outside of my
 mathematical abilities. The thing is, the force is a real force between
 real atoms so it seems like it really should be included in the virial (as
 it certainly is... I checked). I can tell you one thing for sure: the
 effect on box volume is real and noticeable. That is, if you look at the
 average system volume when dd0, it differs in a statistically significant
 manner from the average system volume when dd0 (something that I also
 checked).

 Thank you for looking into this further,
 Chris.

 
 From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se 
 gromacs.org_gmx-users-boun...@maillist.sys.kth.se on behalf of Eudes
 Fileti fil...@gmail.com
 Sent: 24 July 2015 16:47
 To: gromacs.org_gmx-users@maillist.sys.kth.se
 Subject: Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0
 (Eudes Fileti)

 Hello Chris, I write to report the results of the tests you suggested.
 To recap, I have two problems to solve. 1) The bad sampling around z = 0
 and 2) the bumps along to the profile.

 I solved the first discarding all the my initial configurations and
 performing a new pulling (SMD). Only this time I used a higher force
 constant (5000 kJ/mol nm2). Thus I got configurations close to z = 0, where
 they were not generated.

 For the second problem, you suggested recalculate the PMF using double
 precision. The results of this test showed that it does not solve the
 problem, on the contrary the bumps were even more pronounced, as indicated
 by the plot in this link. https://goo.gl/photos/wGNhdyNG9pdqGfcB6

 All tests were performed with prototypes simulations, with 40 windows of 2
 ns spaced by 0.1 nm. A larger sample is obviously necessary for reliable
 profiles, but this was enough to show the trend that I wanted to watch.

 As I have mentioned before, I've done several tests aiming to eliminate
 these bumps: use of higher sampling, up to 20ns per window; reducing the
 spacing between the windows (from 0.1 to 0.05 nm); changing the spring
 constant from 1000 up to 5000 kJ/mol nm2, use of two different versions of
 the Gromacs (4.6 e 5.0) and also I tested it with two different sets of
 initial settings.

 None of this attempts solved the bumps problem.

 If you (or someone else) have any other tips please let me know.

 Thank you
 eef

 ___
 Eudes Eterno Fileti
 Instituto de Ci?ncia e Tecnologia da UNIFESP
 Rua Talim, 330, S?o Jos? dos Campos - SP
 P?gina: sites.google.com/site/fileti/

 
  --
 
  Message: 4
  Date: Wed, 22

Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0 (Eudes Fileti)

[Christopher Neale]

Dear Eudes:

Glad that you solved one of the two issues. As for the bumps in the PMF, I have 
a new theory: the bumps come from pressure coupling. When the sampled distance, 
d, between the two molecules fluctuate a little closer than the center of 
restraint, d0, that adds a repulsive force that contributes to the virial and 
the box gets a little larger. Conversely, slight fluctuations of d that are 
larger than d0 will add a small bias to box contraction. This should be more 
noticeable when the restrained distance involves larger masses.

It is at the moment unclear to me whether this might exert an effect indirectly 
due to overall system density or more directly as coordinate scaling impacts 
the instantaneous value of d. If it is the latter, then semi-isotropic pressure 
coupling, may also enhance the effect since the virial will be computed 
independently along the order parameter (I presume) and hence there is less 
noise from other dimensions.

Can you please try again without pressure coupling (single precision should be 
fine for this test). Hopefully this is not the source of the bumps because, if 
it is affecting the PMF noticeably and the underlying free energy surface has a 
large gradient, then d will always be on one side of d0 and the effect will not 
be merely bumps but also some type of bias in the PMF. Whether this bias is 
accurate or artifactual falls outside of my mathematical abilities. The thing 
is, the force is a real force between real atoms so it seems like it really 
should be included in the virial (as it certainly is... I checked). I can tell 
you one thing for sure: the effect on box volume is real and noticeable. That 
is, if you look at the average system volume when dd0, it differs in a 
statistically significant manner from the average system volume when dd0 
(something that I also checked).

Thank you for looking into this further,
Chris.


From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se 
gromacs.org_gmx-users-boun...@maillist.sys.kth.se on behalf of Eudes Fileti 
fil...@gmail.com
Sent: 24 July 2015 16:47
To: gromacs.org_gmx-users@maillist.sys.kth.se
Subject: Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0 (Eudes 
Fileti)

Hello Chris, I write to report the results of the tests you suggested.
To recap, I have two problems to solve. 1) The bad sampling around z = 0
and 2) the bumps along to the profile.

I solved the first discarding all the my initial configurations and
performing a new pulling (SMD). Only this time I used a higher force
constant (5000 kJ/mol nm2). Thus I got configurations close to z = 0, where
they were not generated.

For the second problem, you suggested recalculate the PMF using double
precision. The results of this test showed that it does not solve the
problem, on the contrary the bumps were even more pronounced, as indicated
by the plot in this link. https://goo.gl/photos/wGNhdyNG9pdqGfcB6

All tests were performed with prototypes simulations, with 40 windows of 2
ns spaced by 0.1 nm. A larger sample is obviously necessary for reliable
profiles, but this was enough to show the trend that I wanted to watch.

As I have mentioned before, I've done several tests aiming to eliminate
these bumps: use of higher sampling, up to 20ns per window; reducing the
spacing between the windows (from 0.1 to 0.05 nm); changing the spring
constant from 1000 up to 5000 kJ/mol nm2, use of two different versions of
the Gromacs (4.6 e 5.0) and also I tested it with two different sets of
initial settings.

None of this attempts solved the bumps problem.

If you (or someone else) have any other tips please let me know.

Thank you
eef

___
Eudes Eterno Fileti
Instituto de Ciência e Tecnologia da UNIFESP
Rua Talim, 330, São José dos Campos - SP
Página: sites.google.com/site/fileti/


 --

 Message: 4
 Date: Wed, 22 Jul 2015 14:56:50 +
 From: Christopher Neale chris.ne...@alum.utoronto.ca
 To: gmx-us...@gromacs.org gmx-us...@gromacs.org
 Subject: Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0
 Message-ID:
 
 blupr03mb18470a33a4e3ff149c95963c5...@blupr03mb184.namprd03.prod.outlook.com
 

 Content-Type: text/plain; charset=iso-8859-1

 Dear Eudes:

 There are two issues: The first issue is the fact that you've got a
 sampling problem near the bilayer center. The second issue is the periodic
 bumps that you see in your PMFs. I'll take the second part first.

 The source of the periodic bumps in PMFs from umbrella sampling is, to me,
 a million dollar question. I've seen them in my own work. I've seen then in
 the literature (as you noted for Fig. 4 in
 http://www.mdpi.com/1422-0067/13/11/14451/htm ). I've seen them when
 people use g_wham and Alan Grossfield's version of WHAM. What I don't yet
 know is if people also see this when running US simulations with AMBER,
 CHARMM, or NAMD. Frankly, either answer scares me

Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0 (Eudes Fileti)

[Eudes Fileti]

Hello Chris, I write to report the results of the tests you suggested.
To recap, I have two problems to solve. 1) The bad sampling around z = 0
and 2) the bumps along to the profile.

I solved the first discarding all the my initial configurations and
performing a new pulling (SMD). Only this time I used a higher force
constant (5000 kJ/mol nm2). Thus I got configurations close to z = 0, where
they were not generated.

For the second problem, you suggested recalculate the PMF using double
precision. The results of this test showed that it does not solve the
problem, on the contrary the bumps were even more pronounced, as indicated
by the plot in this link. https://goo.gl/photos/wGNhdyNG9pdqGfcB6

All tests were performed with prototypes simulations, with 40 windows of 2
ns spaced by 0.1 nm. A larger sample is obviously necessary for reliable
profiles, but this was enough to show the trend that I wanted to watch.

As I have mentioned before, I've done several tests aiming to eliminate
these bumps: use of higher sampling, up to 20ns per window; reducing the
spacing between the windows (from 0.1 to 0.05 nm); changing the spring
constant from 1000 up to 5000 kJ/mol nm2, use of two different versions of
the Gromacs (4.6 e 5.0) and also I tested it with two different sets of
initial settings.

None of this attempts solved the bumps problem.

If you (or someone else) have any other tips please let me know.

Thank you
eef

___
Eudes Eterno Fileti
Instituto de Ciência e Tecnologia da UNIFESP
Rua Talim, 330, São José dos Campos - SP
Página: sites.google.com/site/fileti/


 --

 Message: 4
 Date: Wed, 22 Jul 2015 14:56:50 +
 From: Christopher Neale chris.ne...@alum.utoronto.ca
 To: gmx-us...@gromacs.org gmx-us...@gromacs.org
 Subject: Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0
 Message-ID:
 
 blupr03mb18470a33a4e3ff149c95963c5...@blupr03mb184.namprd03.prod.outlook.com
 

 Content-Type: text/plain; charset=iso-8859-1

 Dear Eudes:

 There are two issues: The first issue is the fact that you've got a
 sampling problem near the bilayer center. The second issue is the periodic
 bumps that you see in your PMFs. I'll take the second part first.

 The source of the periodic bumps in PMFs from umbrella sampling is, to me,
 a million dollar question. I've seen them in my own work. I've seen then in
 the literature (as you noted for Fig. 4 in
 http://www.mdpi.com/1422-0067/13/11/14451/htm ). I've seen them when
 people use g_wham and Alan Grossfield's version of WHAM. What I don't yet
 know is if people also see this when running US simulations with AMBER,
 CHARMM, or NAMD. Frankly, either answer scares me a little. If you see wild
 oscillations of the PMF, at large distances then one possible source is
 that you are near a distance that is half your box length along the order
 parameter. Note that with constant pressure simulations you will get
 oscillations in the length of the box and also when your membrane changes
 shape it could flip the vector of closest approach by 180 deg if you are
 close to the half-box limit. However, that should not be relevant to the
 bumps (out of interest, how large is your box along z?). Although I do
  n't know what is going on with these PMF bumps, I also note that
 membranes as a whole always tend to migrate toward positive z and lipids
 tend to flow to positive x in gromacs simulations, so I wonder if it is a
 rounding issue. Could you try again with double precision and see if you
 get the bumps?

 As for the problem with sampling near the bilayer center... my first guess
 is that you've got some of your replicas on the wrong side of the bilayer's
 center. Did you intend to go across the center and sample also in the lower
 leaflet? I've only ever used gromacs 3 and 4 to do pulling simulations,
 never gmx 5. You can see my concerns about gmx5 for this type of issue near
 the bilayer center here:
 https://www.mail-archive.com/gromacs.org_gmx-users%40maillist.sys.kth.se/msg11324.html
 One simply has to test it. However, if gmx5 does indeed work properly with
 this new US philosophy, then I presume that you simply need to move your
 starting coordinates such that your solute is in the positive leaflet for
 all replicas. You can test this by visualization or g_dist, which reports
 the sign of the displacement (look in the 5th column I think for the z
 value). Note that you are using pull_start=yes, so which side of the
 bilayer your solute is initially on should make a difference here.

 Chris.

 -- original message:

 Hi Chris, a few days ago I posted a question on GMX list but unfortunately
 I not received an answer yet. So I write to you for help at your
 convenience.
 http://permalink.gmane.org/gmane.science.biology.gromacs.user/78439

 Besides the problem exposed the link above I'm trying to understand the
 importance of the relative distance between the COM. Due to fluctuation in
 the position

Re: [gmx-users] PMF using umbrella sampling and Gromacs 5.0

[Christopher Neale]

Dear Eudes:

There are two issues: The first issue is the fact that you've got a sampling 
problem near the bilayer center. The second issue is the periodic bumps that 
you see in your PMFs. I'll take the second part first.

The source of the periodic bumps in PMFs from umbrella sampling is, to me, a 
million dollar question. I've seen them in my own work. I've seen then in the 
literature (as you noted for Fig. 4 in 
http://www.mdpi.com/1422-0067/13/11/14451/htm ). I've seen them when people use 
g_wham and Alan Grossfield's version of WHAM. What I don't yet know is if 
people also see this when running US simulations with AMBER, CHARMM, or NAMD. 
Frankly, either answer scares me a little. If you see wild oscillations of the 
PMF, at large distances then one possible source is that you are near a 
distance that is half your box length along the order parameter. Note that with 
constant pressure simulations you will get oscillations in the length of the 
box and also when your membrane changes shape it could flip the vector of 
closest approach by 180 deg if you are close to the half-box limit. However, 
that should not be relevant to the bumps (out of interest, how large is your 
box along z?). Although I don't know what is going on with these PMF bumps, I 
also note that membranes as a whole always tend to migrate toward positive z 
and lipids tend to flow to positive x in gromacs simulations, so I wonder if it 
is a rounding issue. Could you try again with double precision and see if you 
get the bumps?

As for the problem with sampling near the bilayer center... my first guess is 
that you've got some of your replicas on the wrong side of the bilayer's 
center. Did you intend to go across the center and sample also in the lower 
leaflet? I've only ever used gromacs 3 and 4 to do pulling simulations, never 
gmx 5. You can see my concerns about gmx5 for this type of issue near the 
bilayer center here: 
https://www.mail-archive.com/gromacs.org_gmx-users%40maillist.sys.kth.se/msg11324.html
One simply has to test it. However, if gmx5 does indeed work properly with this 
new US philosophy, then I presume that you simply need to move your starting 
coordinates such that your solute is in the positive leaflet for all replicas. 
You can test this by visualization or g_dist, which reports the sign of the 
displacement (look in the 5th column I think for the z value). Note that you 
are using pull_start=yes, so which side of the bilayer your solute is initially 
on should make a difference here.

Chris.
 
-- original message:

Hi Chris, a few days ago I posted a question on GMX list but unfortunately I 
not received an answer yet. So I write to you for help at your convenience.
http://permalink.gmane.org/gmane.science.biology.gromacs.user/78439

Besides the problem exposed the link above I'm trying to understand the 
importance of the relative distance between the COM. Due to fluctuation in the 
position of the center of mass position of the membrane, the minimum distance 
is never zero, as shown in the graphs of my pulling below. What is the effect 
of this difference in the calculation of the PMF? Could this be the source of 
my problem?
https://goo.gl/photos/cwwLzog6wXAgVJG88

Bests
eef

PS. I found this paper below where authors have published this unusual behavior 
(Figure 4). They did not explain the reason for the oscillations at large 
distances and I also do not know why this occurs.
http://www.mdpi.com/1422-0067/13/11/14451/htm




From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se 
gromacs.org_gmx-users-boun...@maillist.sys.kth.se on behalf of Eudes Fileti 
fil...@gmail.com
Sent: 18 July 2015 21:06
To: gmx-us...@gromacs.org
Subject: [gmx-users] PMF using umbrella sampling and Gromacs 5.0

Hello guys, I'm trying to calculate the PMF using umbrella sampling for a
small molecule to penetrate a lipid membrane. The 1D reaction coordinate is
along the z axis, which corresponds to the bilayer normal. The umbrella
potential acts on the center of mass of the molecule. The initial
configurations for each window, separated by a distance of 0.1nm, in a
range of 4 nm (distance between the centers of mass of the membrane and the
molecule), were obtained by a SMD.

The umbrella potential was applied according to the parameters below (for
Gromacs version 5.0.3). Each window was sampled by 5 ns.

; COM PULLING
pull = umbrella
pull_geometry= direction
pull_dim = N N Y
pull_start   = yes
pull-print-reference = no
pull_nstxout = 1000
pull_nstfout = 1000
pull_ngroups = 2
pull-ncoords = 1
; Group name, weight (default all 1), vector, init, rate (nm/ps),
kJ/(mol*nm^2)
pull-group1-name = DPPC ;  ref
pull-group2-name = LIG ;  pulled
pull-coord1-groups   = 1  2
pull-coord1-origin   = 0 0 0
pull-coord1-vec  = 0 0 1
pull-coord1

[gmx-users] PMF using umbrella sampling and Gromacs 5.0

[Eudes Fileti]

Hello guys, I'm trying to calculate the PMF using umbrella sampling for a
small molecule to penetrate a lipid membrane. The 1D reaction coordinate is
along the z axis, which corresponds to the bilayer normal. The umbrella
potential acts on the center of mass of the molecule. The initial
configurations for each window, separated by a distance of 0.1nm, in a
range of 4 nm (distance between the centers of mass of the membrane and the
molecule), were obtained by a SMD.

The umbrella potential was applied according to the parameters below (for
Gromacs version 5.0.3). Each window was sampled by 5 ns.

; COM PULLING
pull = umbrella
pull_geometry= direction
pull_dim = N N Y
pull_start   = yes
pull-print-reference = no
pull_nstxout = 1000
pull_nstfout = 1000
pull_ngroups = 2
pull-ncoords = 1
; Group name, weight (default all 1), vector, init, rate (nm/ps),
kJ/(mol*nm^2)
pull-group1-name = DPPC ;  ref
pull-group2-name = LIG ;  pulled
pull-coord1-groups   = 1  2
pull-coord1-origin   = 0 0 0
pull-coord1-vec  = 0 0 1
pull-coord1-init = 0
pull-coord1-rate = 0.0
pull-coord1-k= 3000

Histograms and the PMF obtained are shown in figure the link below.
https://goo.gl/photos/RkW9gbWrgeKEfV3R7

I repeated the same test using other parameters (larger and small k values)
and options (cylinder and position, for this later I have used gmx 4.6) and
so far I could not get a satisfactory profile. In all tests, a problem that
I have observed is that the region near z = 0 is not sampled (there is a
gap between 0.0 and 0.5 nm). In addition the profile presents not smooth,
but somehow oscillating mainly for large z.

As the gmx distance give a value different of zero for the smallest
distance of separation between the centers of mass (around 0.1-0.2 nm) I
believe that this weird behavior is related to the reference distance that
I have used.

Could someone give me a light? Most of the tips I read in GMX list are
related to previous versions of the Gromacs and in a way the other tips
were already included in my tests.

Thank you
eef

___
Eudes Eterno Fileti
Instituto de Ciência e Tecnologia da UNIFESP
Rua Talim, 330, São José dos Campos - SP
Página: sites.google.com/site/fileti/
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Re: [gmx-users] PMF calculation with constraint distance

[Justin Lemkul]

On 5/21/15 5:19 PM, leila salimi wrote:

Thanks Justin. Yes I have done PMF with Blue moon ensemble with DFT. Now I
want to do the same with gromacs to have some knowledge  about my FF
parameters and compare with my DFT results!
You meant I have to do with different configuration and average the forces?
I am wondering that I did in DFT for each constrained distances around 15
ps MD and then I used averaged forces for each distances!



I don't know what your QM involved; when I hear Blue moon I think of the 
beverage - cheers! :)


If your QM gave you an energy vs. time plot, that's not a PMF.  That's a 
potential energy scan with some fixed intermolecular geometry.  Again, maybe I 
just don't know what you're doing.  In principle you could do the same thing 
with a rigid constraint between the groups, but your post is a bit confusing.


-Justin

--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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[gmx-users] PMF calculation with constraint distance

[leila salimi]

Hi all,

I started to calculate PMF between two ions in solution and I
used constraint for pull option, instead of umbrella as I saw in Umbrella
sampling Tutorial of Justin.

This is the part of my mdp file!
; Pull code
pull= constraint; Justin's value was umbrella
pull_geometry   = distance  ; simple distance increase
pull_dim= Y Y Y
pull_start  = no; Justin's value was yes
pull_ngroups= 1
pull_group0 = CA_surf
pull_group1 = carboxylate_carbon
pull_init1  = 0.288 ; initial distance between pulling groups
pull_rate1  = 0.001 ; 0.001 nm per ps
pull_k1 = 1000  ; kJ mol^-1 nm^-2

I got the output  and I tried to pull out with increasing  the distance
between two atoms and I have pullf.xvg file!

I know that I can have the time evolution of constrained distance with
g_dist from xtc file! I am wondering how to have the distance with
corresponding constrained force?
If I have the file contain forces and distances, I can integrate the force
then I will have PMF.

Could you help me that how I can manage this?
Regards,
Leila
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Re: [gmx-users] PMF calculation with constraint distance

[Justin Lemkul]

On 5/21/15 5:00 PM, leila salimi wrote:

Hi all,

I started to calculate PMF between two ions in solution and I
used constraint for pull option, instead of umbrella as I saw in Umbrella
sampling Tutorial of Justin.

This is the part of my mdp file!
; Pull code
pull= constraint; Justin's value was umbrella
pull_geometry   = distance  ; simple distance increase
pull_dim= Y Y Y
pull_start  = no; Justin's value was yes
pull_ngroups= 1
pull_group0 = CA_surf
pull_group1 = carboxylate_carbon
pull_init1  = 0.288 ; initial distance between pulling groups
pull_rate1  = 0.001 ; 0.001 nm per ps
pull_k1 = 1000  ; kJ mol^-1 nm^-2

I got the output  and I tried to pull out with increasing  the distance
between two atoms and I have pullf.xvg file!

I know that I can have the time evolution of constrained distance with
g_dist from xtc file! I am wondering how to have the distance with
corresponding constrained force?
If I have the file contain forces and distances, I can integrate the force
then I will have PMF.



This probably won't give you a very reliable PMF.  You're effectively trying to 
use the Jarzynski method (albeit with a constraint rather than a harmonic 
potential) with one run (normally you have to do this many, many times), which 
won't give a correct result.



Could you help me that how I can manage this?


If you have the constraint force in pullf.xvg and the distance in another .xvg 
file, it's just a matter of using grep/awk to combine the two.  Whether or not 
this means anything is another matter.  Getting a PMF between ions is trivially 
simple with a harmonic potential.


-Justin

--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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Re: [gmx-users] PMF calculation with constraint distance

[leila salimi]

Thanks Justin. Yes I have done PMF with Blue moon ensemble with DFT. Now I
want to do the same with gromacs to have some knowledge  about my FF
parameters and compare with my DFT results!
You meant I have to do with different configuration and average the forces?
I am wondering that I did in DFT for each constrained distances around 15
ps MD and then I used averaged forces for each distances!

Cheers,
Leila

On Thu, May 21, 2015 at 11:04 PM, Justin Lemkul jalem...@vt.edu wrote:



 On 5/21/15 5:00 PM, leila salimi wrote:

 Hi all,

 I started to calculate PMF between two ions in solution and I
 used constraint for pull option, instead of umbrella as I saw in Umbrella
 sampling Tutorial of Justin.

 This is the part of my mdp file!
 ; Pull code
 pull= constraint; Justin's value was umbrella
 pull_geometry   = distance  ; simple distance increase
 pull_dim= Y Y Y
 pull_start  = no; Justin's value was yes
 pull_ngroups= 1
 pull_group0 = CA_surf
 pull_group1 = carboxylate_carbon
 pull_init1  = 0.288 ; initial distance between pulling groups
 pull_rate1  = 0.001 ; 0.001 nm per ps
 pull_k1 = 1000  ; kJ mol^-1 nm^-2

 I got the output  and I tried to pull out with increasing  the distance
 between two atoms and I have pullf.xvg file!

 I know that I can have the time evolution of constrained distance with
 g_dist from xtc file! I am wondering how to have the distance with
 corresponding constrained force?
 If I have the file contain forces and distances, I can integrate the force
 then I will have PMF.


 This probably won't give you a very reliable PMF.  You're effectively
 trying to use the Jarzynski method (albeit with a constraint rather than a
 harmonic potential) with one run (normally you have to do this many, many
 times), which won't give a correct result.

  Could you help me that how I can manage this?


 If you have the constraint force in pullf.xvg and the distance in another
 .xvg file, it's just a matter of using grep/awk to combine the two.
 Whether or not this means anything is another matter.  Getting a PMF
 between ions is trivially simple with a harmonic potential.

 -Justin

 --
 ==

 Justin A. Lemkul, Ph.D.
 Ruth L. Kirschstein NRSA Postdoctoral Fellow

 Department of Pharmaceutical Sciences
 School of Pharmacy
 Health Sciences Facility II, Room 629
 University of Maryland, Baltimore
 20 Penn St.
 Baltimore, MD 21201

 jalem...@outerbanks.umaryland.edu | (410) 706-7441
 http://mackerell.umaryland.edu/~jalemkul

 ==
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Re: [gmx-users] PMF calculation by umbrella sampling simulations

[Justin Lemkul]

On 4/30/15 4:12 PM, MPI wrote:

Hi Justin,

Thanks for your explanation.
(1)
In the tutorial, then what is a good approximate value of free energy
?  if  one follows the protocol.   Is -37 or so kcal mol^-1  ?



That is what you should get from the tutorial.


Here, 26 windows of COM distances are used, each for 10 ns simulation.

(2)
In your original paper,  -50.5 kcal mol^-1 is the free energy for
dissociation of a single peptide from protofibril.
In this full preparation,  you used 31-window setup, each for 10 ns simulation.

I've been aware of the difference between 26 and 31 windows but  questions are

First,  if one obtains a reasonable histogram like

https://docs.google.com/file/d/0B9uTAq1wCc1fVkRPY2FrTExFcmM/edit

,how can one  tell whether if  the system needs more windows ?
because these overlap windows look appropriate.



Simply looking at histograms only tells you if you're in the ballpark.  g_wham 
has a very nice set of options for doing error analysis.  You'll note there is 
minimal overlap in a few of your windows; these would correspond to regions of 
the reaction coordinate with large error.  If you do the bootstrap analysis you 
will see this.



Second,   after full preparation, how did you know the free energy of
-50.5 or so  is a  GOOD value ?



I did error analysis :)  See details in the paper.


Third,  comparing  a coarse ( the tutorial) with a full preparation (
your original paper),  it is somehow unclear that the number of
windows can cause  a significant difference of 13 kcal mol^-1 since
it runs independently for 10 ns in each window.

Please see  PMF curve attached in a simulation of  26 windows, each for 10 ns.

https://drive.google.com/open?id=0B9uTAq1wCc1fSUtwSVh4cnFpZVEauthuser=0

The PMF curve looks reasonable except  when it converges to 37.5 kcal
mol^-1 or so.


There is no clear energy minimum there and you haven't done error analysis, so 
looks good doesn't really mean anything.


-Justin

--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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Re: [gmx-users] PMF calculation by umbrella sampling simulations

[MPI]

Hi Justin,

   Thanks for your explanation.
(1)
In the tutorial, then what is a good approximate value of free energy
?  if  one follows the protocol.   Is -37 or so kcal mol^-1  ?

Here, 26 windows of COM distances are used, each for 10 ns simulation.

(2)
In your original paper,  -50.5 kcal mol^-1 is the free energy for
dissociation of a single peptide from protofibril.
In this full preparation,  you used 31-window setup, each for 10 ns simulation.

I've been aware of the difference between 26 and 31 windows but  questions are

First,  if one obtains a reasonable histogram like

https://docs.google.com/file/d/0B9uTAq1wCc1fVkRPY2FrTExFcmM/edit

,how can one  tell whether if  the system needs more windows ?
because these overlap windows look appropriate.

Second,   after full preparation, how did you know the free energy of
-50.5 or so  is a  GOOD value ?

Third,  comparing  a coarse ( the tutorial) with a full preparation (
your original paper),  it is somehow unclear that the number of
windows can cause  a significant difference of 13 kcal mol^-1 since
it runs independently for 10 ns in each window.

Please see  PMF curve attached in a simulation of  26 windows, each for 10 ns.

https://drive.google.com/open?id=0B9uTAq1wCc1fSUtwSVh4cnFpZVEauthuser=0

The PMF curve looks reasonable except  when it converges to 37.5 kcal
mol^-1 or so.


Thanks,

Dewey

Justin Lemkul wrote:
 On 4/30/15 12:43 AM, MPI wrote:
Dear Users,
 
 With GMX 4.6.5, I tried to reproduce a system of the dissociation of
  a single peptide in an AB42 protofibril with PMF (potential of mean
  force) calculation in Justin's umbrella sampling tutorial.  He
  derived the binding energy from PMF from a series of umbrella sampling
  simulations and obtained a value of  free energy  close to  -50.5
  kcal mol-1.   But I got a value of -37.5 kcal mol-1 after PMF
  curve was converged.  The value difference is significant and this
  raises two questions.  What dose cause this difference of  ~13 kcal mol
  -1  ?  although I used  GPU for calculations, which is the only
  modification (cutoff-scheme = Verlet).  What is a reasonable range of
  binding free energy in this case of AB42 protofibril ?
 
 As I state in the tutorial and as I have said multiple times on the list (even
 just a few days ago!), you will not produce the PMF profile shown in the
 tutorial unless you follow the exact protocol in the paper (which is linked in
 the tutorial).  The value of -37 or so is what you will achieve if you do what
 the tutorial says, which is a quick and dirty approximation of the protocol.
 The full preparation (100 ns of MD on the protofibril, followed by a special
 window setup described in the paper to adequately sample small COM distances)
 will yield the quoted value.
 -Justin
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[gmx-users] PMF calculation by umbrella sampling simulations

[MPI]

 Dear Users,

  With GMX 4.6.5, I tried to reproduce a system of the dissociation of
a single peptide in an AB42 protofibril with PMF (potential of mean
force) calculation in Justin's umbrella sampling tutorial.  He
derived the binding energy from PMF from a series of umbrella sampling
simulations and obtained a value of  free energy  close to  -50.5
kcal mol-1.   But I got a value of -37.5 kcal mol-1 after PMF
curve was converged.  The value difference is significant and this
raises two questions.  What dose cause this difference of  ~13 kcal mol
-1  ?  although I used  GPU for calculations, which is the only
modification (cutoff-scheme = Verlet).  What is a reasonable range of
binding free energy in this case of AB42 protofibril ?

The umbrella histogram showing the overlap between window looks
reasonable. See attached here.

https://drive.google.com/open?id=0B9uTAq1wCc1fVkRPY2FrTExFcmMauthuser=0

Suggestions or opinions are appreciated.

Thanks,
Dewey
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Re: [gmx-users] PMF and RDF

[Justin Lemkul]

On 12/9/14 11:51 PM, sujithkakkat . wrote:

Hi Erik and Justin,

   Thanks for the response.

   Erik, I was thinking that in the case of hydrophobic solutes, there is a
higher chance of proper sampling of all points along the inter solute
distance. I believe the water shell around the hydrophibic solvent can
break easier than the that in the case of ions. In that case I hope
standard simulations can give better solute-solute RDFs and PMF may be
avoided. The article which I refered to studies hydrophobic solutes and
they have done PMF calculations.



This may work, but again it assumes that the energy barriers are relatively low 
and that the force field is sufficiently balanced against solute-water 
interactions that these transitions happen in an unbiased manner.  There's 
probably no way to know a priori whether or not it will work, but it's quick to 
find out.  For what it's worth, PMFs between small molecules are very cheap to 
compute, unlike larger macromolecular complexes, so there's only minimal gain by 
doing things this way.


-Justin

--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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Re: [gmx-users] PMF and RDF

[Erik Marklund]

Dear Sujith,

Umbrella sampling does exactly that, but adds a biasing potential to sample 
high-energy regions of the reaction coordinate in separate simulations. The -px 
output when you do umbrella sampling with mdrun is indeed a sampling of 
distances along the reaction coordinate, which if you histogram it is the rdf. 
g_wham uses that data (or alternatively the force along the reaction coordinate 
instead of the distance) to build a PMF. My question to you is why do you think 
rdfs are significantly easier than pmfs?

Kind regards,
Erik

On 9 Dec 2014, at 06:39, sujithkakkat . sujithk...@gmail.com wrote:

 Dear all,
 
 I read in *Phys. Chem. Chem. Phys., 2009, 11, 10427-10437*, that the
 radial distribution function is directly related to Potential of mean force
 through RDF=exp(-PMF/kT).
 
 My question is why would someone worry about computing PMF in a simple
 case like interaction between two small solute molecules in water , along
 the intermolecular distance, when one can get the RDF between the solutes ,
 which I believe is easier than PMF calculation.
 
  Another article *Biophysical Chemistry 101-102 (2002), 295-307 *reports
 PMF between solute molecules from Monte Carlo simulations. Why not just
 find RDF.
 
 Regards,
 
 Sujith.
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Re: [gmx-users] PMF and RDF

[Justin Lemkul]

On 12/9/14 1:39 AM, sujithkakkat . wrote:

Dear all,

  I read in *Phys. Chem. Chem. Phys., 2009, 11, 10427-10437*, that the
radial distribution function is directly related to Potential of mean force
through RDF=exp(-PMF/kT).

  My question is why would someone worry about computing PMF in a simple
case like interaction between two small solute molecules in water , along
the intermolecular distance, when one can get the RDF between the solutes ,
which I believe is easier than PMF calculation.

   Another article *Biophysical Chemistry 101-102 (2002), 295-307 *reports
PMF between solute molecules from Monte Carlo simulations. Why not just
find RDF.



For some systems, this may work, but only if the barriers are small enough that 
they can be sampled during normal MD.  For instance, we recently compared PMFs 
from umbrella sampling and from RDF for ions in water.  Given that the waters 
rarely displace from the ions' solvation shells (11 kcal/mol barrier in one 
case, for instance), there is a region with complete absence of sampling.  So, 
in some cases it may work, and in others (likely many) it will fail for 
practical reasons.


-Justin

--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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Re: [gmx-users] PMF and RDF

[Erik Marklund]

On 9 Dec 2014, at 11:00, Erik Marklund erik.markl...@chem.ox.ac.uk wrote:

 Dear Sujith,
 
 Umbrella sampling does exactly that, but adds a biasing potential to sample 
 high-energy regions of the reaction coordinate in separate simulations. The 
 -px output when you do umbrella sampling with mdrun is indeed a sampling of 
 distances along the reaction coordinate, which if you histogram it is the 
 rdf. g_wham uses that data (or alternatively the force along the reaction 
 coordinate instead of the distance) to build a PMF. My question to you is why 
 do you think rdfs are significantly easier than pmts?

To clarify what I meant, in light of what Justin wrote earlier, is that the pmf 
and ref can *in principle* be calculated from exactly the same data. The 
*conventional* way to get the pmf involves biasing the simulations to sample 
poorly populated regions, whereas the rdf is commonly inferred from simulations 
without such bias. In principle the rdf can also be obtained from biased 
simulations if that bias is corrected for during analysis, and similarly a pmf 
can be obtained without bias. As Justin said, there are many situations where 
the sampling is insufficient for some distances however.

Erik

 

 Kind regards,
 Erik
 
 On 9 Dec 2014, at 06:39, sujithkakkat . sujithk...@gmail.com wrote:
 
 Dear all,
 
I read in *Phys. Chem. Chem. Phys., 2009, 11, 10427-10437*, that the
 radial distribution function is directly related to Potential of mean force
 through RDF=exp(-PMF/kT).
 
My question is why would someone worry about computing PMF in a simple
 case like interaction between two small solute molecules in water , along
 the intermolecular distance, when one can get the RDF between the solutes ,
 which I believe is easier than PMF calculation.
 
 Another article *Biophysical Chemistry 101-102 (2002), 295-307 *reports
 PMF between solute molecules from Monte Carlo simulations. Why not just
 find RDF.
 
 Regards,
 
 Sujith.
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Re: [gmx-users] PMF and RDF

[sujithkakkat .]

Hi Erik and Justin,

  Thanks for the response.

  Erik, I was thinking that in the case of hydrophobic solutes, there is a
higher chance of proper sampling of all points along the inter solute
distance. I believe the water shell around the hydrophibic solvent can
break easier than the that in the case of ions. In that case I hope
standard simulations can give better solute-solute RDFs and PMF may be
avoided. The article which I refered to studies hydrophobic solutes and
they have done PMF calculations.

Regards,
Sujith.

On Tue, Dec 9, 2014 at 7:41 PM, Erik Marklund erik.markl...@chem.ox.ac.uk
wrote:


 On 9 Dec 2014, at 11:00, Erik Marklund erik.markl...@chem.ox.ac.uk
 wrote:

  Dear Sujith,
 
  Umbrella sampling does exactly that, but adds a biasing potential to
 sample high-energy regions of the reaction coordinate in separate
 simulations. The -px output when you do umbrella sampling with mdrun is
 indeed a sampling of distances along the reaction coordinate, which if you
 histogram it is the rdf. g_wham uses that data (or alternatively the force
 along the reaction coordinate instead of the distance) to build a PMF. My
 question to you is why do you think rdfs are significantly easier than pmts?

 To clarify what I meant, in light of what Justin wrote earlier, is that
 the pmf and ref can *in principle* be calculated from exactly the same
 data. The *conventional* way to get the pmf involves biasing the
 simulations to sample poorly populated regions, whereas the rdf is commonly
 inferred from simulations without such bias. In principle the rdf can also
 be obtained from biased simulations if that bias is corrected for during
 analysis, and similarly a pmf can be obtained without bias. As Justin said,
 there are many situations where the sampling is insufficient for some
 distances however.

 Erik

 

  Kind regards,
  Erik
 
  On 9 Dec 2014, at 06:39, sujithkakkat . sujithk...@gmail.com wrote:
 
  Dear all,
 
 I read in *Phys. Chem. Chem. Phys., 2009, 11, 10427-10437*, that the
  radial distribution function is directly related to Potential of mean
 force
  through RDF=exp(-PMF/kT).
 
 My question is why would someone worry about computing PMF in a
 simple
  case like interaction between two small solute molecules in water ,
 along
  the intermolecular distance, when one can get the RDF between the
 solutes ,
  which I believe is easier than PMF calculation.
 
  Another article *Biophysical Chemistry 101-102 (2002), 295-307
 *reports
  PMF between solute molecules from Monte Carlo simulations. Why not just
  find RDF.
 
  Regards,
 
  Sujith.
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[gmx-users] PMF and RDF

[sujithkakkat .]

Dear all,

 I read in *Phys. Chem. Chem. Phys., 2009, 11, 10427-10437*, that the
radial distribution function is directly related to Potential of mean force
through RDF=exp(-PMF/kT).

 My question is why would someone worry about computing PMF in a simple
case like interaction between two small solute molecules in water , along
the intermolecular distance, when one can get the RDF between the solutes ,
which I believe is easier than PMF calculation.

  Another article *Biophysical Chemistry 101-102 (2002), 295-307 *reports
PMF between solute molecules from Monte Carlo simulations. Why not just
find RDF.

Regards,

Sujith.
-- 
Gromacs Users mailing list

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Re: [gmx-users] PMF curve in umbrella sampling

[Justin Lemkul]

On 8/30/14, 8:09 AM, Mana Ib wrote:

Thankyou for your response. I spaced them at approx 0.05nm because at the
473rd configuration my ligand becomes solvated...and completely dissociated
from the protein and there is a jump in the COM distances. Would you
recommend running windows for configurations beyond 473 to get an accurate
PMF curve?

COM distances:

01.2500689
11.2390118
21.2656376
31.2382807
41.2464908
51.2613748
61.2571518
71.2494564
81.2383828
91.2645215
101.2555224
111.2915937
121.2589550
131.2495953
141.2489617
151.2657266
161.2611536
171.2734816
181.2627461
191.2537713
201.2643420
211.2796929
221.2557689
231.2522986
241.2710813
251.2805812
261.2488314
271.2324920
281.2218119
291.2351364
301.254
311.2607237
321.2823184
331.2744044
341.2816412
351.2946619
361.2658573
371.2778631
381.2684767
391.2577963
401.2658514
411.2675236
421.2645024
431.2517917
441.2668618
451.2837279
461.2711920
471.2984477
481.2850081
491.2738078
501.2791895
511.2671049
521.2689266
531.2527233
541.2541883
551.2683328
561.2879772
571.2765738
581.2745949
591.2624943
601.2713360
611.2903701
621.2538780
631.2524761
641.2804133
651.2904843
661.2767571
671.2811158
681.2873763
691.2897247
701.2967854
711.2898058
721.2866045
731.2680842
741.2828430
751.2517999
761.2789755
771.2674298
781.2963352
791.2863842
801.2686276
811.2527305
821.2675610
831.2817050
841.2519698
851.2547150
861.2316085
871.2301512
881.2587688
891.2676184
901.2682347
911.2762364
921.2774154
931.2711686
941.2815300
951.3117696
961.3037083
971.2877588
981.3003120
991.2830641
1001.2736199
1011.2975351
1021.2716285
1031.2636745
1041.2595536
1051.2820042
1061.2727789
1071.2464533
1081.2609475
1091.2909839
1101.2857704
1111.2857469
1121.2838980
1131.2866713
1141.2899315
1151.2773947
1161.2701035
1171.2897719
1181.2819400
1191.3044168
1201.2997466
1211.2958813
1221.2790420
1231.2786862
1241.2843164
1251.3100673
1261.2898589
1271.2878088
1281.2788408
1291.2817291
1301.2892330
1311.2841049
1321.2907283
1331.2960732
1341.2822367
1351.3024569
1361.2965143
1371.2839130
1381.2765539
1391.2846087
1401.2716116
1411.2829932
1421.2692751
1431.3112148
1441.3305217
1451.3154910
1461.2995077
1471.2961320
1481.3201323
1491.3076353
1501.3050537
1511.3059070
1521.3154420
1531.2943887
1541.3121384
1551.3134962
1561.3178825
1571.3217572
1581.2944893
1591.2979667
1601.2917393
1611.2989479
1621.3068420
1631.3138773
1641.2800533
1651.2904462
1661.2946355
1671.2841026
1681.2830913
1691.2916815
1701.3171769
1711.2839959
1721.2902473
1731.3021219
1741.3086892
1751.3062795
1761.2896782
1771.2646221
1781.2967244
1791.3318710
1801.3260037
1811.3066446
1821.3087828
1831.3031635
1841.2651044
1851.3077284
1861.2997077
1871.2937896
1881.3135617
1891.3186882
1901.3199843
1911.3641998
1921.3608552
1931.3191408
1941.3369676
1951.3495121
1961.3608030
1971.3640209
1981.3769726
1991.3143706
2001.3277380
2011.3327760
2021.3275329
2031.3249296
2041.3207476
2051.3446074
2061.3251934
2071.3521178
2081.3415477
2091.3205338
2101.3183049
2111.3279040
2121.3370273
2131.3558873
2141.3275462
2151.3397077
2161.3265324
2171.3250760
2181.3557339
2191.3370665
2201.3299704
2211.3431152
2221.3304195
2231.3742563
2241.3224043
2251.3176907
2261.3264394
2271.3246692
2281.3441764
2291.3347285
2301.3389533
2311.3308688
2321.3257663
2331.3243916
2341.3384953
2351.3148066
2361.2998172
2371.3078777
2381.3343482
2391.3064271
2401.3530262
2411.3190423
2421.3246952
2431.3256948
2441.3378791
2451.3348513
2461.3224670
2471.3466573
2481.3461218
2491.3204277
2501.3261340
2511.3477811
2521.3435458
2531.3670396
2541.3363574
2551.3268965
2561.3046312
2571.3266972
2581.3626263
2591.3708274
2601.3452878
2611.3339913
2621.3417501
2631.3323883
2641.3441674
2651.3532716
2661.3320799
2671.3409791
2681.3437917
2691.3395978
2701.3411486
2711.3256128
2721.3365294
2731.3508692
2741.3467736
2751.3287274
2761.3815287
2771.3535491
2781.3791600
279 

Re: [gmx-users] PMF curve in umbrella sampling

[Mana Ib]

Thankyou for your response. I spaced them at approx 0.05nm because at the
473rd configuration my ligand becomes solvated...and completely dissociated
from the protein and there is a jump in the COM distances. Would you
recommend running windows for configurations beyond 473 to get an accurate
PMF curve?

COM distances:

01.2500689
11.2390118
21.2656376
31.2382807
41.2464908
51.2613748
61.2571518
71.2494564
81.2383828
91.2645215
101.2555224
111.2915937
121.2589550
131.2495953
141.2489617
151.2657266
161.2611536
171.2734816
181.2627461
191.2537713
201.2643420
211.2796929
221.2557689
231.2522986
241.2710813
251.2805812
261.2488314
271.2324920
281.2218119
291.2351364
301.254
311.2607237
321.2823184
331.2744044
341.2816412
351.2946619
361.2658573
371.2778631
381.2684767
391.2577963
401.2658514
411.2675236
421.2645024
431.2517917
441.2668618
451.2837279
461.2711920
471.2984477
481.2850081
491.2738078
501.2791895
511.2671049
521.2689266
531.2527233
541.2541883
551.2683328
561.2879772
571.2765738
581.2745949
591.2624943
601.2713360
611.2903701
621.2538780
631.2524761
641.2804133
651.2904843
661.2767571
671.2811158
681.2873763
691.2897247
701.2967854
711.2898058
721.2866045
731.2680842
741.2828430
751.2517999
761.2789755
771.2674298
781.2963352
791.2863842
801.2686276
811.2527305
821.2675610
831.2817050
841.2519698
851.2547150
861.2316085
871.2301512
881.2587688
891.2676184
901.2682347
911.2762364
921.2774154
931.2711686
941.2815300
951.3117696
961.3037083
971.2877588
981.3003120
991.2830641
1001.2736199
1011.2975351
1021.2716285
1031.2636745
1041.2595536
1051.2820042
1061.2727789
1071.2464533
1081.2609475
1091.2909839
1101.2857704
1111.2857469
1121.2838980
1131.2866713
1141.2899315
1151.2773947
1161.2701035
1171.2897719
1181.2819400
1191.3044168
1201.2997466
1211.2958813
1221.2790420
1231.2786862
1241.2843164
1251.3100673
1261.2898589
1271.2878088
1281.2788408
1291.2817291
1301.2892330
1311.2841049
1321.2907283
1331.2960732
1341.2822367
1351.3024569
1361.2965143
1371.2839130
1381.2765539
1391.2846087
1401.2716116
1411.2829932
1421.2692751
1431.3112148
1441.3305217
1451.3154910
1461.2995077
1471.2961320
1481.3201323
1491.3076353
1501.3050537
1511.3059070
1521.3154420
1531.2943887
1541.3121384
1551.3134962
1561.3178825
1571.3217572
1581.2944893
1591.2979667
1601.2917393
1611.2989479
1621.3068420
1631.3138773
1641.2800533
1651.2904462
1661.2946355
1671.2841026
1681.2830913
1691.2916815
1701.3171769
1711.2839959
1721.2902473
1731.3021219
1741.3086892
1751.3062795
1761.2896782
1771.2646221
1781.2967244
1791.3318710
1801.3260037
1811.3066446
1821.3087828
1831.3031635
1841.2651044
1851.3077284
1861.2997077
1871.2937896
1881.3135617
1891.3186882
1901.3199843
1911.3641998
1921.3608552
1931.3191408
1941.3369676
1951.3495121
1961.3608030
1971.3640209
1981.3769726
1991.3143706
2001.3277380
2011.3327760
2021.3275329
2031.3249296
2041.3207476
2051.3446074
2061.3251934
2071.3521178
2081.3415477
2091.3205338
2101.3183049
2111.3279040
2121.3370273
2131.3558873
2141.3275462
2151.3397077
2161.3265324
2171.3250760
2181.3557339
2191.3370665
2201.3299704
2211.3431152
2221.3304195
2231.3742563
2241.3224043
2251.3176907
2261.3264394
2271.3246692
2281.3441764
2291.3347285
2301.3389533
2311.3308688
2321.3257663
2331.3243916
2341.3384953
2351.3148066
2361.2998172
2371.3078777
2381.3343482
2391.3064271
2401.3530262
2411.3190423
2421.3246952
2431.3256948
2441.3378791
2451.3348513
2461.3224670
2471.3466573
2481.3461218
2491.3204277
2501.3261340
2511.3477811
2521.3435458
2531.3670396
2541.3363574
2551.3268965
2561.3046312
2571.3266972
2581.3626263
2591.3708274
2601.3452878
2611.3339913
2621.3417501
2631.3323883
2641.3441674
2651.3532716
2661.3320799
2671.3409791
2681.3437917
2691.3395978
2701.3411486
2711.3256128
2721.3365294
2731.3508692
2741.3467736
2751.3287274
2761.3815287
2771.3535491
2781.3791600
2791.3642347
2801.3533387
281

[gmx-users] PMF curve in umbrella sampling

[Mana Ib]

Dear Users,

I am doing an umbrella sampling for a protein-ligand complex, wherein I
first did an SMD run for 500 ps and generated 500 configurations, the COM
distances for these configurations start at 1.25nm for conf0 and so on till
6.4nm for conf500. Hence I used a 0.05nm spacing to select configurations
for the umbrella sampling windows.
I have currently completed running 2 windows, each window was subjected to
a 5ns  mdrun.

This is my mdp file parameters

title   = Umbrella pulling simulation
define  = -DPOSRES
; Run parameters
integrator  = md
dt  = 0.002
tinit   = 0
nsteps  = 250   ; 5 ns
nstcomm = 10
; Output parameters
nstxout = 5 ; every 100 ps
nstvout = 5
nstfout = 5000
nstxtcout   = 5000  ; every 10 ps
nstenergy   = 5000
; Bond parameters
constraint_algorithm= lincs
constraints = all-bonds
continuation= yes
; Single-range cutoff scheme
nstlist = 5
ns_type = grid
rlist   = 1.4
rcoulomb= 1.4
rvdw= 1.4
; PME electrostatics parameters
coulombtype = PME
fourierspacing  = 0.12
fourier_nx  = 0
fourier_ny  = 0
fourier_nz  = 0
pme_order   = 4
ewald_rtol  = 1e-5
optimize_fft= yes
; Berendsen temperature coupling is on in two groups
Tcoupl  = Nose-Hoover
tc_grps = Protein   Non-Protein
tau_t   = 0.5   0.5
ref_t   = 310   310
; Pressure coupling is on
Pcoupl  = Parrinello-Rahman
pcoupltype  = isotropic
tau_p   = 1.0
compressibility = 4.5e-5
ref_p   = 1.0
refcoord_scaling = com
; Generate velocities is off
gen_vel = no
; Periodic boundary conditions are on in all directions
pbc = xyz
; Long-range dispersion correction
DispCorr= EnerPres
; Pull code
pull= umbrella
pull_geometry   = distance
pull_dim= Y N N
pull_start  = yes
pull_ngroups= 1
pull_group0 = Chain_A
pull_group1 = NL
pull_init1  = 0
pull_rate1  = 0.0
pull_k1 = 500  ; kJ mol^-1 nm^-2
pull_nstxout= 1000  ; every 2 ps
pull_nstfout= 1000  ; every 2 ps


When I use g_wham to plot the histogram and PMF curve for these 2 windows,
my plots don't seem to follow the general trend as given in
tutorials..(figure links below). Is this discrepancy because I have used
only files from 2 windows to plot these? Or are these due to some other
errors in the protocol?

http://i46.photobucket.com/albums/f121/fullmeasure29/histo_2win_zpsff19fe60.png

http://i46.photobucket.com/albums/f121/fullmeasure29/pmf_2win_zps04adb8f7.png
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Re: [gmx-users] PMF curve in umbrella sampling

[Justin Lemkul]

On 8/29/14, 2:08 PM, Mana Ib wrote:

Dear Users,

I am doing an umbrella sampling for a protein-ligand complex, wherein I
first did an SMD run for 500 ps and generated 500 configurations, the COM
distances for these configurations start at 1.25nm for conf0 and so on till
6.4nm for conf500. Hence I used a 0.05nm spacing to select configurations
for the umbrella sampling windows.
I have currently completed running 2 windows, each window was subjected to
a 5ns  mdrun.

This is my mdp file parameters

title   = Umbrella pulling simulation
define  = -DPOSRES
; Run parameters
integrator  = md
dt  = 0.002
tinit   = 0
nsteps  = 250   ; 5 ns
nstcomm = 10
; Output parameters
nstxout = 5 ; every 100 ps
nstvout = 5
nstfout = 5000
nstxtcout   = 5000  ; every 10 ps
nstenergy   = 5000
; Bond parameters
constraint_algorithm= lincs
constraints = all-bonds
continuation= yes
; Single-range cutoff scheme
nstlist = 5
ns_type = grid
rlist   = 1.4
rcoulomb= 1.4
rvdw= 1.4
; PME electrostatics parameters
coulombtype = PME
fourierspacing  = 0.12
fourier_nx  = 0
fourier_ny  = 0
fourier_nz  = 0
pme_order   = 4
ewald_rtol  = 1e-5
optimize_fft= yes
; Berendsen temperature coupling is on in two groups
Tcoupl  = Nose-Hoover
tc_grps = Protein   Non-Protein
tau_t   = 0.5   0.5
ref_t   = 310   310
; Pressure coupling is on
Pcoupl  = Parrinello-Rahman
pcoupltype  = isotropic
tau_p   = 1.0
compressibility = 4.5e-5
ref_p   = 1.0
refcoord_scaling = com
; Generate velocities is off
gen_vel = no
; Periodic boundary conditions are on in all directions
pbc = xyz
; Long-range dispersion correction
DispCorr= EnerPres
; Pull code
pull= umbrella
pull_geometry   = distance
pull_dim= Y N N
pull_start  = yes
pull_ngroups= 1
pull_group0 = Chain_A
pull_group1 = NL
pull_init1  = 0
pull_rate1  = 0.0
pull_k1 = 500  ; kJ mol^-1 nm^-2
pull_nstxout= 1000  ; every 2 ps
pull_nstfout= 1000  ; every 2 ps


When I use g_wham to plot the histogram and PMF curve for these 2 windows,
my plots don't seem to follow the general trend as given in
tutorials..(figure links below). Is this discrepancy because I have used
only files from 2 windows to plot these? Or are these due to some other
errors in the protocol?

http://i46.photobucket.com/albums/f121/fullmeasure29/histo_2win_zpsff19fe60.png

http://i46.photobucket.com/albums/f121/fullmeasure29/pmf_2win_zps04adb8f7.png



The two windows yield effectively overlapping distributions and a meaningless 
PMF.  Space the windows further (0.05 nm is very tight) and run more windows for 
a real PMF as a function of a meaningful reaction coordinate.


-Justin

--
==

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 601
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==
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[gmx-users] PMF calculation with three reaction coordinates

[liaoxyi]

Dear gromacs users,
  I am running an umbrella pulling to calculate the PMF of a soft protein 
adsorbed on surface. Since the protein is soft (easy to deform),  I conducted 
three pull groups on the COM (center of mass) of three domains of the protein. 
The pullings are all along the z axis but on different initial positions. So it 
outputs three Position variables in the pull-x.xvg and also three Force 
variables in the pull-f.xvg as follows:
@xaxis  label Time (ps)
@yaxis  label Position (nm)
@ s0 legend 1 dZ
@ s1 legend 2 dZ
@ s2 legend 3 dZ
0.3.756993.739154.94193
0.50003.73193.709284.94322
1.3.72363.707454.91479

  My problem is to calculate the PMF with three reaction coordinates. By 
default, all pull groups found in all pullx/pullf files are used in WHAM. But, 
in this way, it disturbs the PMF curve along the z axis. In GMX 5.0, the g_wham 
-is groupsel.dat can decide which pull groups are used. My confusions are:
1. It is right to choose only one or two pull groups for the PMF when there are 
actually three pullings conducted?
   Obviously, the PMF curve differs a lot with one, two, or three pull groups.
2. Can the final PMF value for protein desorption be the sum of the PMF of each 
pull group?
   Calculate the PMF with only one pull group with g_wham -is first, then add 
the three PMF values together.
Which way should be right to calculate the PMF of protein desorption?
Is there a better solution for that?
I need your advices badly.
Thank you very much !


 Mabel

PS: the pulling settings in md.mdp
; COM PULLING 
pull = umbrella
pull_geometry= distance
pull_dim = N N Y 
pull_start   = yes
pull-print-reference = no
pull_nstxout = 250
pull_nstfout = 250
pull_ngroups = 3; three pull groups, not including the 
absolute referece group
pull-ncoords = 3; three pull coordinates
; Group name, weight (default all 1), vector, init, rate (nm/ps), kJ/(mol*nm^2)
pull-group1-name = Backbone__r_1-17 ;  resid 1-17
pull-coord1-groups   = 0  1
pull-coord1-origin   = 3.3 3.2 1.0   ; half the box a, b
pull-coord1-vec  = 0.0 0.0 0.0
pull-coord1-init = 0  
pull-coord1-rate = 0.0  
pull-coord1-k= 4184  

pull-group2-name = Backbone__r_18-39
pull-coord2-groups   = 0  2
pull-coord2-origin   = 3.3 3.2 1.0
pull-coord2-vec  = 0.0 0.0 0.0
pull-coord2-init = 0  
pull-coord2-rate = 0.0  
pull-coord2-k= 4184  

pull-group3-name = Backbone__r_40-51
pull-coord3-groups   = 0  3
pull-coord3-origin   = 3.3 3.2 1.0
pull-coord3-vec  = 0.0 0.0 0.0
pull-coord3-init = 0  
pull-coord3-rate = 0.0  
pull-coord3-k= 4184  

 


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[gmx-users] PMF plot against distance

[Arunima Shilpi]

Dear Sir

I have been working in umbrella sampling to analyse protein-ligand
interaction and
calculate Potential Mean Force (PMF).
I have generated the following his.xvg file and have provided in the
attachment. I request you to kindly guide me as to how to plot against
distance.

I also have the query as to how far the result obtain is correct.

Regards

Arunima
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