Re: [gmx-users] PMF decompostion

[Justin Lemkul]

On 12/5/16 6:36 AM, Salman Zarrini wrote:

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} ... .



Perturbing the Hamiltonian as a function of lambda is more informative than what 
it sounded like you were talking about.  If one wants to do, e.g. a FEP 
calculation within each window and separate out various terms, that might be 
useful.  Simply calculating interaction energies is not.  My main point was 
cautionary - many force fields do not ascribe physical significance to the 
individual contributions, and pretty much all force fields are built on the 
concept of cancellation of errors.  With CHARMM, we try to get a reasonable 
balance and we use free energy of hydration as target data when possible after 
establishing the electrostatic parameters (charges) based on QM water 
interactions.  So the balance is pretty good, in general, aside from the few 
instances where NBFIX has to clean up some issues, whether they arise from the 
additive functional form itself (a fundamental limitation) or the combination rules.



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?



Everything is dictated by the force field.  So naturally, any molecule-water 
interaction is involved because these forces, in turn, play a role in how much 
work the biasing potential has to do in each window.


-Justin


Thanks,

Salman Zarrini


On Mon, Dec 5, 2016 at 12:07 AM, Justin Lemkul  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 

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  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 > >
>> 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 
 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 

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 
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 
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

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/Mailing_Lists/GMX-Users_List before posting!

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--
==

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

Department of Pharmaceutical Sciences
School of 

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 
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 
>> 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
> 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 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 
 on behalf of Salman Zarrini 

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 
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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 
 on behalf of Salman Zarrini 

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
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