Re: [gmx-users] ligand moving out during umbrella sampling

[Justin Lemkul]

On 5/22/17 4:04 AM, abhisek Mondal wrote:

I have used active site residues COM for this time with Ligand COM. As a
test case. r 6-10 | r 78-80 | r 56 | r 63 | r 35 gave me my custom group of
residues belonging to active site. Using both the COMs now I calculated the
vector PL (protein-ligand) and applied as pull-coord1-vec.
However, I hate to say, after 500-600ps md_umbrella run the ligand got out
of the active site again. It is becoming very painful.
As you asked lastly, due to flexible ligand scenario. I'm further thinking
not to use ligand COM, despite coordinate of some atoms near the ring
structure. However, I'm totally confused regarding whether this approach
will work out. Giving it a try though.



If your ligand is large and flexible or the protein rotates very quickly, then 
it will be hard to define the reaction coordinate in the manner that we've been 
trying.  You may have to move to something more generic like distance geometry 
with pull_dim = Y Y Y and a very large box (obviously computationally expensive) 
or you'll have to calculate the binding free energy another way entirely 
(alchemical transformation, MM/PBSA, etc).


-Justin




On Sun, May 21, 2017 at 8:39 PM, abhisek Mondal 
wrote:


Beg your pardon, I have not ignored your comment entirely regarding using
specific residue COM. I just recently succeeded performing md_umbrella
simulation (using protein COM) on few configurations.
.
I have not used specific residues COM so far as because of some confusions
regrading defining it. The residue stretch is not continuous e.g. residue
6-10, 78-80, 56, 63, 35 are to be active site residue. I got no idea how to
define such discrete set of residues using make_ndx command.



On Sun, May 21, 2017 at 8:13 PM, Justin Lemkul  wrote:




On 5/21/17 9:47 AM, abhisek Mondal wrote:


I did try the code successfully on a configuration generated after
pulling.
The NVT approach with direction-periodic geometry worked nicely for the
particular configuration.

However, when I tried to reapply the same code (with modified COMs and
thus
pull_vec) on a different configuration, something awkward happened. The
ligand got pulled through protein and got stuck inside it. I have put the
trajectory movie alongwith md_umbrella.mdp file here:
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

Would you please care to give some advise regarding this odd behavior.



Likely some elements of your setup are inadequate.  You have a large,
flexible ligand, so perhaps using its overall COM is inappropriate.  You're
also using the entire protein COM as the other end of the reaction
coordinate, and perhaps that's not good enough (I've suggested a number of
times to be judicious in the choice of residues taken as the group
corresponding to the protein, but it seems you're simply not doing that so
I'll stop suggesting it).  Perhaps your pull vector is calculated
incorrectly.  A lot going on.  Back up and do something simpler, a test
case that is easy to define so you can get comfortable with setting these
things up and understanding/diagnosing weird behavior.

-Justin


Thank you.


On Fri, May 19, 2017 at 5:18 PM, Justin Lemkul  wrote:




On 5/19/17 5:56 AM, abhisek Mondal wrote:

On Thu, May 18, 2017 at 6:48 PM, Justin Lemkul  wrote:





On 5/17/17 8:55 AM, abhisek Mondal wrote:

This time I think I got ligand restrained successfully during the


umbrella
sampling. I have removed the restrain from protein, as per your
advice.
Defined the COM vector in md_umbrella.mdp, applied pull_k1=1000 and
used
pull_rate1=0.0.
I have uploaded the trajectory movie (and other mdp files) in the
following
link:
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

However, I'm facing a problem. Due to the withdrawal of the position
restrain of protein. The protein and ligand (together) is moving
around
the
box and resulting in "Distance of pull group 1 (10.441990 nm) is
larger
than 0.49 times the box size (10.646989)" error.

As per the video I have uploaded, if I assume this approach worked,
then
how can I avoid this error ? Is  there any way to make sure the
protein-ligand remains in the middle of the box (or nearby). I have
taken
pretty large box compared to the protein structure from the
beginning.

Please suggest me a way out.


Use a larger box or use direction-periodic geometry.






 For the sake of computational power I'm leaning towards
direction-periodic
geometry. However, from the mailing list entries I found out that
pressure
coupling should not be used for this kind of geometry setup.
NVT coupling with no velocity generation is what I'm opting for. There
are
a lot of doubt regarding the md_umbrella.mdp setup using NVT protocol.
Would you please suggest if the code (
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0)
looks
sensible ?

Eagerly waiting for your opinion.


Try it and see what happens.

Re: [gmx-users] ligand moving out during umbrella sampling

[abhisek Mondal]

I have used active site residues COM for this time with Ligand COM. As a
test case. r 6-10 | r 78-80 | r 56 | r 63 | r 35 gave me my custom group of
residues belonging to active site. Using both the COMs now I calculated the
vector PL (protein-ligand) and applied as pull-coord1-vec.
However, I hate to say, after 500-600ps md_umbrella run the ligand got out
of the active site again. It is becoming very painful.
As you asked lastly, due to flexible ligand scenario. I'm further thinking
not to use ligand COM, despite coordinate of some atoms near the ring
structure. However, I'm totally confused regarding whether this approach
will work out. Giving it a try though.



On Sun, May 21, 2017 at 8:39 PM, abhisek Mondal 
wrote:

> Beg your pardon, I have not ignored your comment entirely regarding using
> specific residue COM. I just recently succeeded performing md_umbrella
> simulation (using protein COM) on few configurations.
> .
> I have not used specific residues COM so far as because of some confusions
> regrading defining it. The residue stretch is not continuous e.g. residue
> 6-10, 78-80, 56, 63, 35 are to be active site residue. I got no idea how to
> define such discrete set of residues using make_ndx command.
>
>
>
> On Sun, May 21, 2017 at 8:13 PM, Justin Lemkul  wrote:
>
>>
>>
>> On 5/21/17 9:47 AM, abhisek Mondal wrote:
>>
>>> I did try the code successfully on a configuration generated after
>>> pulling.
>>> The NVT approach with direction-periodic geometry worked nicely for the
>>> particular configuration.
>>>
>>> However, when I tried to reapply the same code (with modified COMs and
>>> thus
>>> pull_vec) on a different configuration, something awkward happened. The
>>> ligand got pulled through protein and got stuck inside it. I have put the
>>> trajectory movie alongwith md_umbrella.mdp file here:
>>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>>>
>>> Would you please care to give some advise regarding this odd behavior.
>>>
>>>
>> Likely some elements of your setup are inadequate.  You have a large,
>> flexible ligand, so perhaps using its overall COM is inappropriate.  You're
>> also using the entire protein COM as the other end of the reaction
>> coordinate, and perhaps that's not good enough (I've suggested a number of
>> times to be judicious in the choice of residues taken as the group
>> corresponding to the protein, but it seems you're simply not doing that so
>> I'll stop suggesting it).  Perhaps your pull vector is calculated
>> incorrectly.  A lot going on.  Back up and do something simpler, a test
>> case that is easy to define so you can get comfortable with setting these
>> things up and understanding/diagnosing weird behavior.
>>
>> -Justin
>>
>>
>> Thank you.
>>>
>>> On Fri, May 19, 2017 at 5:18 PM, Justin Lemkul  wrote:
>>>
>>>

 On 5/19/17 5:56 AM, abhisek Mondal wrote:

 On Thu, May 18, 2017 at 6:48 PM, Justin Lemkul  wrote:
>
>
>
>> On 5/17/17 8:55 AM, abhisek Mondal wrote:
>>
>> This time I think I got ligand restrained successfully during the
>>
>>> umbrella
>>> sampling. I have removed the restrain from protein, as per your
>>> advice.
>>> Defined the COM vector in md_umbrella.mdp, applied pull_k1=1000 and
>>> used
>>> pull_rate1=0.0.
>>> I have uploaded the trajectory movie (and other mdp files) in the
>>> following
>>> link:
>>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>>>
>>> However, I'm facing a problem. Due to the withdrawal of the position
>>> restrain of protein. The protein and ligand (together) is moving
>>> around
>>> the
>>> box and resulting in "Distance of pull group 1 (10.441990 nm) is
>>> larger
>>> than 0.49 times the box size (10.646989)" error.
>>>
>>> As per the video I have uploaded, if I assume this approach worked,
>>> then
>>> how can I avoid this error ? Is  there any way to make sure the
>>> protein-ligand remains in the middle of the box (or nearby). I have
>>> taken
>>> pretty large box compared to the protein structure from the
>>> beginning.
>>>
>>> Please suggest me a way out.
>>>
>>>
>>> Use a larger box or use direction-periodic geometry.
>>>
>>
>>
>
>  For the sake of computational power I'm leaning towards
> direction-periodic
> geometry. However, from the mailing list entries I found out that
> pressure
> coupling should not be used for this kind of geometry setup.
> NVT coupling with no velocity generation is what I'm opting for. There
> are
> a lot of doubt regarding the md_umbrella.mdp setup using NVT protocol.
> Would you please suggest if the code (
> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0)
> looks
> sensible ?
>
> Eagerly waiting for your 

Re: [gmx-users] ligand moving out during umbrella sampling

[abhisek Mondal]

Beg your pardon, I have not ignored your comment entirely regarding using
specific residue COM. I just recently succeeded performing md_umbrella
simulation (using protein COM) on few configurations.
.
I have not used specific residues COM so far as because of some confusions
regrading defining it. The residue stretch is not continuous e.g. residue
6-10, 78-80, 56, 63, 35 are to be active site residue. I got no idea how to
define such discrete set of residues using make_ndx command.



On Sun, May 21, 2017 at 8:13 PM, Justin Lemkul  wrote:

>
>
> On 5/21/17 9:47 AM, abhisek Mondal wrote:
>
>> I did try the code successfully on a configuration generated after
>> pulling.
>> The NVT approach with direction-periodic geometry worked nicely for the
>> particular configuration.
>>
>> However, when I tried to reapply the same code (with modified COMs and
>> thus
>> pull_vec) on a different configuration, something awkward happened. The
>> ligand got pulled through protein and got stuck inside it. I have put the
>> trajectory movie alongwith md_umbrella.mdp file here:
>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>>
>> Would you please care to give some advise regarding this odd behavior.
>>
>>
> Likely some elements of your setup are inadequate.  You have a large,
> flexible ligand, so perhaps using its overall COM is inappropriate.  You're
> also using the entire protein COM as the other end of the reaction
> coordinate, and perhaps that's not good enough (I've suggested a number of
> times to be judicious in the choice of residues taken as the group
> corresponding to the protein, but it seems you're simply not doing that so
> I'll stop suggesting it).  Perhaps your pull vector is calculated
> incorrectly.  A lot going on.  Back up and do something simpler, a test
> case that is easy to define so you can get comfortable with setting these
> things up and understanding/diagnosing weird behavior.
>
> -Justin
>
>
> Thank you.
>>
>> On Fri, May 19, 2017 at 5:18 PM, Justin Lemkul  wrote:
>>
>>
>>>
>>> On 5/19/17 5:56 AM, abhisek Mondal wrote:
>>>
>>> On Thu, May 18, 2017 at 6:48 PM, Justin Lemkul  wrote:



> On 5/17/17 8:55 AM, abhisek Mondal wrote:
>
> This time I think I got ligand restrained successfully during the
>
>> umbrella
>> sampling. I have removed the restrain from protein, as per your
>> advice.
>> Defined the COM vector in md_umbrella.mdp, applied pull_k1=1000 and
>> used
>> pull_rate1=0.0.
>> I have uploaded the trajectory movie (and other mdp files) in the
>> following
>> link:
>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>>
>> However, I'm facing a problem. Due to the withdrawal of the position
>> restrain of protein. The protein and ligand (together) is moving
>> around
>> the
>> box and resulting in "Distance of pull group 1 (10.441990 nm) is
>> larger
>> than 0.49 times the box size (10.646989)" error.
>>
>> As per the video I have uploaded, if I assume this approach worked,
>> then
>> how can I avoid this error ? Is  there any way to make sure the
>> protein-ligand remains in the middle of the box (or nearby). I have
>> taken
>> pretty large box compared to the protein structure from the beginning.
>>
>> Please suggest me a way out.
>>
>>
>> Use a larger box or use direction-periodic geometry.
>>
>
>

  For the sake of computational power I'm leaning towards
 direction-periodic
 geometry. However, from the mailing list entries I found out that
 pressure
 coupling should not be used for this kind of geometry setup.
 NVT coupling with no velocity generation is what I'm opting for. There
 are
 a lot of doubt regarding the md_umbrella.mdp setup using NVT protocol.
 Would you please suggest if the code (
 https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0)
 looks
 sensible ?

 Eagerly waiting for your opinion.


 Try it and see what happens.
>>>
>>> -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 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
>>> 

Re: [gmx-users] ligand moving out during umbrella sampling

[Justin Lemkul]

On 5/21/17 9:47 AM, abhisek Mondal wrote:

I did try the code successfully on a configuration generated after pulling.
The NVT approach with direction-periodic geometry worked nicely for the
particular configuration.

However, when I tried to reapply the same code (with modified COMs and thus
pull_vec) on a different configuration, something awkward happened. The
ligand got pulled through protein and got stuck inside it. I have put the
trajectory movie alongwith md_umbrella.mdp file here:
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

Would you please care to give some advise regarding this odd behavior.



Likely some elements of your setup are inadequate.  You have a large, flexible 
ligand, so perhaps using its overall COM is inappropriate.  You're also using 
the entire protein COM as the other end of the reaction coordinate, and perhaps 
that's not good enough (I've suggested a number of times to be judicious in the 
choice of residues taken as the group corresponding to the protein, but it seems 
you're simply not doing that so I'll stop suggesting it).  Perhaps your pull 
vector is calculated incorrectly.  A lot going on.  Back up and do something 
simpler, a test case that is easy to define so you can get comfortable with 
setting these things up and understanding/diagnosing weird behavior.


-Justin


Thank you.

On Fri, May 19, 2017 at 5:18 PM, Justin Lemkul  wrote:




On 5/19/17 5:56 AM, abhisek Mondal wrote:


On Thu, May 18, 2017 at 6:48 PM, Justin Lemkul  wrote:




On 5/17/17 8:55 AM, abhisek Mondal wrote:

This time I think I got ligand restrained successfully during the

umbrella
sampling. I have removed the restrain from protein, as per your advice.
Defined the COM vector in md_umbrella.mdp, applied pull_k1=1000 and used
pull_rate1=0.0.
I have uploaded the trajectory movie (and other mdp files) in the
following
link:
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

However, I'm facing a problem. Due to the withdrawal of the position
restrain of protein. The protein and ligand (together) is moving around
the
box and resulting in "Distance of pull group 1 (10.441990 nm) is larger
than 0.49 times the box size (10.646989)" error.

As per the video I have uploaded, if I assume this approach worked, then
how can I avoid this error ? Is  there any way to make sure the
protein-ligand remains in the middle of the box (or nearby). I have
taken
pretty large box compared to the protein structure from the beginning.

Please suggest me a way out.


Use a larger box or use direction-periodic geometry.





 For the sake of computational power I'm leaning towards
direction-periodic
geometry. However, from the mailing list entries I found out that pressure
coupling should not be used for this kind of geometry setup.
NVT coupling with no velocity generation is what I'm opting for. There are
a lot of doubt regarding the md_umbrella.mdp setup using NVT protocol.
Would you please suggest if the code (
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0)
looks
sensible ?

Eagerly waiting for your opinion.



Try it and see what happens.

-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 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

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

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mail to gmx-users-requ...@gromacs.org.

Re: [gmx-users] ligand moving out during umbrella sampling

[abhisek Mondal]

I did try the code successfully on a configuration generated after pulling.
The NVT approach with direction-periodic geometry worked nicely for the
particular configuration.

However, when I tried to reapply the same code (with modified COMs and thus
pull_vec) on a different configuration, something awkward happened. The
ligand got pulled through protein and got stuck inside it. I have put the
trajectory movie alongwith md_umbrella.mdp file here:
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

Would you please care to give some advise regarding this odd behavior.

Thank you.

On Fri, May 19, 2017 at 5:18 PM, Justin Lemkul  wrote:

>
>
> On 5/19/17 5:56 AM, abhisek Mondal wrote:
>
>> On Thu, May 18, 2017 at 6:48 PM, Justin Lemkul  wrote:
>>
>>
>>>
>>> On 5/17/17 8:55 AM, abhisek Mondal wrote:
>>>
>>> This time I think I got ligand restrained successfully during the
 umbrella
 sampling. I have removed the restrain from protein, as per your advice.
 Defined the COM vector in md_umbrella.mdp, applied pull_k1=1000 and used
 pull_rate1=0.0.
 I have uploaded the trajectory movie (and other mdp files) in the
 following
 link:
 https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

 However, I'm facing a problem. Due to the withdrawal of the position
 restrain of protein. The protein and ligand (together) is moving around
 the
 box and resulting in "Distance of pull group 1 (10.441990 nm) is larger
 than 0.49 times the box size (10.646989)" error.

 As per the video I have uploaded, if I assume this approach worked, then
 how can I avoid this error ? Is  there any way to make sure the
 protein-ligand remains in the middle of the box (or nearby). I have
 taken
 pretty large box compared to the protein structure from the beginning.

 Please suggest me a way out.


 Use a larger box or use direction-periodic geometry.
>>>
>>
>>
>>  For the sake of computational power I'm leaning towards
>> direction-periodic
>> geometry. However, from the mailing list entries I found out that pressure
>> coupling should not be used for this kind of geometry setup.
>> NVT coupling with no velocity generation is what I'm opting for. There are
>> a lot of doubt regarding the md_umbrella.mdp setup using NVT protocol.
>> Would you please suggest if the code (
>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0)
>> looks
>> sensible ?
>>
>> Eagerly waiting for your opinion.
>>
>>
> Try it and see what happens.
>
> -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 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.
>



-- 
Abhisek Mondal

*Senior Research Fellow*

*Structural Biology and Bioinformatics Division*
*CSIR-Indian Institute of Chemical Biology*

*Kolkata 700032*

*INDIA*
-- 
Gromacs Users mailing list

* Please search the archive at 
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mail to gmx-users-requ...@gromacs.org.

Re: [gmx-users] ligand moving out during umbrella sampling

[Justin Lemkul]

On 5/19/17 5:56 AM, abhisek Mondal wrote:

On Thu, May 18, 2017 at 6:48 PM, Justin Lemkul  wrote:




On 5/17/17 8:55 AM, abhisek Mondal wrote:


This time I think I got ligand restrained successfully during the umbrella
sampling. I have removed the restrain from protein, as per your advice.
Defined the COM vector in md_umbrella.mdp, applied pull_k1=1000 and used
pull_rate1=0.0.
I have uploaded the trajectory movie (and other mdp files) in the
following
link:
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

However, I'm facing a problem. Due to the withdrawal of the position
restrain of protein. The protein and ligand (together) is moving around
the
box and resulting in "Distance of pull group 1 (10.441990 nm) is larger
than 0.49 times the box size (10.646989)" error.

As per the video I have uploaded, if I assume this approach worked, then
how can I avoid this error ? Is  there any way to make sure the
protein-ligand remains in the middle of the box (or nearby). I have taken
pretty large box compared to the protein structure from the beginning.

Please suggest me a way out.



Use a larger box or use direction-periodic geometry.



 For the sake of computational power I'm leaning towards direction-periodic
geometry. However, from the mailing list entries I found out that pressure
coupling should not be used for this kind of geometry setup.
NVT coupling with no velocity generation is what I'm opting for. There are
a lot of doubt regarding the md_umbrella.mdp setup using NVT protocol.
Would you please suggest if the code (
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0) looks
sensible ?

Eagerly waiting for your opinion.



Try it and see what happens.

-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 
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.

Re: [gmx-users] ligand moving out during umbrella sampling

[abhisek Mondal]

On Thu, May 18, 2017 at 6:48 PM, Justin Lemkul  wrote:

>
>
> On 5/17/17 8:55 AM, abhisek Mondal wrote:
>
>> This time I think I got ligand restrained successfully during the umbrella
>> sampling. I have removed the restrain from protein, as per your advice.
>> Defined the COM vector in md_umbrella.mdp, applied pull_k1=1000 and used
>> pull_rate1=0.0.
>> I have uploaded the trajectory movie (and other mdp files) in the
>> following
>> link:
>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>>
>> However, I'm facing a problem. Due to the withdrawal of the position
>> restrain of protein. The protein and ligand (together) is moving around
>> the
>> box and resulting in "Distance of pull group 1 (10.441990 nm) is larger
>> than 0.49 times the box size (10.646989)" error.
>>
>> As per the video I have uploaded, if I assume this approach worked, then
>> how can I avoid this error ? Is  there any way to make sure the
>> protein-ligand remains in the middle of the box (or nearby). I have taken
>> pretty large box compared to the protein structure from the beginning.
>>
>> Please suggest me a way out.
>>
>>
> Use a larger box or use direction-periodic geometry.


 For the sake of computational power I'm leaning towards direction-periodic
geometry. However, from the mailing list entries I found out that pressure
coupling should not be used for this kind of geometry setup.
NVT coupling with no velocity generation is what I'm opting for. There are
a lot of doubt regarding the md_umbrella.mdp setup using NVT protocol.
Would you please suggest if the code (
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0) looks
sensible ?

Eagerly waiting for your opinion.



>
> -Justin
>
>
> On Mon, May 15, 2017 at 5:48 PM, Justin Lemkul  wrote:
>>
>>
>>>
>>> On 5/15/17 2:45 AM, abhisek Mondal wrote:
>>>
>>> On Thu, May 11, 2017 at 9:03 PM, Justin Lemkul  wrote:



> On 5/11/17 9:21 AM, abhisek Mondal wrote:
>
> On Thu, May 11, 2017 at 11:02 AM, abhisek Mondal <
> abhisek.m...@gmail.com
>
>>
>>> wrote:
>>
>> Hi,
>>
>>
>>> Thank you for the explanation. It really cleared some concepts. But
>>> I'm
>>> still having my ligand moving in this step. I have modified the code
>>> as:
>>> ; Pull code
>>> pull= umbrella
>>> pull_ngroups= 1
>>> pull_group0 = Protein_chain_A
>>> pull_group1 = ACO
>>> pull_geometry   = direction ; simple distance increase
>>> pull_dim   = Y Y Y ; not to allow ligand move along
>>> other
>>> dir
>>> pull_rate1 = 0.0
>>> pull_k1   = 1000   ; kJ mol^-1 nm^-2
>>> pull_start   = yes   ; define initial COM distance > 0
>>> pull_vec1   = 0 0 -1
>>>
>>>
>>> Note that with "direction" geometry, only pull_vec1 is acting.
>>>
>> pull_dim
> is ignored.
>
> The ligand was previously moving along x,y direction when I was using
>
> pull_dim  = N N Y. So I changed it to Y in all direction and provided 0
>>
>>> as
>>> vector  and pull_rate1=0.0, so that it does not move much. But at the
>>> end
>>> of a 10ns run, I see that the ligand is still moving as it was
>>> earlier.
>>>
>>> It shows me:
>>>
>>>  Pull group  natoms  pbc atom  distance at start reference at t=0
>>0  1132936665
>>159  1618  -1.555-1.555
>> Is it ok withe negative value ? Anyway this setup is not working.
>>
>>
>> Again you're trying to just apply the restraint to one dimension and
>> it
>>
> looks to be fairly arbitrary.  I already suggested using the vector
> connecting the ligand COM with the binding site residues' COM and using
> that as pull_vec1.  Draw it out.  It makes a lot more sense than trying
> to
> restrain only along one axis, which as I have said before, makes no
> sense
> in this case.
>
> Thank you for such detailed suggestion.
>
> I followed on as per your suggestion. Calculated COM of protein and
 Ligand.
 Calculated protein-lig vector (using COM) to be used for pulling (as
 pull_vec1).
 Pulling also achieved successfully.
 But after pulling, when I performed the brief npt_umbrella run with
 pull_rate1=0, I found the ligand is moving little bit. Could not
 understand
 what I have mistaken this time.
 So I moved on for umbrella sampling mdrun step, with pull_rate1=0 and
 pull_vec1=as determined from COM calculations. Despite I found that the
 ligand is moving vigorously and got pulled away probably.
 I'm putting npt_umbrella.mdp,md_umbrella.mdp,conf140.gro(used for
 npt_umbrella), npt140.gro,md_umbrella run video in the following link:
 

Re: [gmx-users] ligand moving out during umbrella sampling

[Justin Lemkul]

On 5/17/17 8:55 AM, abhisek Mondal wrote:

This time I think I got ligand restrained successfully during the umbrella
sampling. I have removed the restrain from protein, as per your advice.
Defined the COM vector in md_umbrella.mdp, applied pull_k1=1000 and used
pull_rate1=0.0.
I have uploaded the trajectory movie (and other mdp files) in the following
link:
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

However, I'm facing a problem. Due to the withdrawal of the position
restrain of protein. The protein and ligand (together) is moving around the
box and resulting in "Distance of pull group 1 (10.441990 nm) is larger
than 0.49 times the box size (10.646989)" error.

As per the video I have uploaded, if I assume this approach worked, then
how can I avoid this error ? Is  there any way to make sure the
protein-ligand remains in the middle of the box (or nearby). I have taken
pretty large box compared to the protein structure from the beginning.

Please suggest me a way out.



Use a larger box or use direction-periodic geometry.

-Justin


On Mon, May 15, 2017 at 5:48 PM, Justin Lemkul  wrote:




On 5/15/17 2:45 AM, abhisek Mondal wrote:


On Thu, May 11, 2017 at 9:03 PM, Justin Lemkul  wrote:




On 5/11/17 9:21 AM, abhisek Mondal wrote:

On Thu, May 11, 2017 at 11:02 AM, abhisek Mondal  0
pull_vec1   = 0 0 -1


Note that with "direction" geometry, only pull_vec1 is acting.

pull_dim
is ignored.

The ligand was previously moving along x,y direction when I was using


pull_dim  = N N Y. So I changed it to Y in all direction and provided 0

as
vector  and pull_rate1=0.0, so that it does not move much. But at the
end
of a 10ns run, I see that the ligand is still moving as it was earlier.

It shows me:


 Pull group  natoms  pbc atom  distance at start reference at t=0
   0  1132936665
   159  1618  -1.555-1.555
Is it ok withe negative value ? Anyway this setup is not working.


Again you're trying to just apply the restraint to one dimension and it

looks to be fairly arbitrary.  I already suggested using the vector
connecting the ligand COM with the binding site residues' COM and using
that as pull_vec1.  Draw it out.  It makes a lot more sense than trying
to
restrain only along one axis, which as I have said before, makes no sense
in this case.

Thank you for such detailed suggestion.


I followed on as per your suggestion. Calculated COM of protein and
Ligand.
Calculated protein-lig vector (using COM) to be used for pulling (as
pull_vec1).
Pulling also achieved successfully.
But after pulling, when I performed the brief npt_umbrella run with
pull_rate1=0, I found the ligand is moving little bit. Could not
understand
what I have mistaken this time.
So I moved on for umbrella sampling mdrun step, with pull_rate1=0 and
pull_vec1=as determined from COM calculations. Despite I found that the
ligand is moving vigorously and got pulled away probably.
I'm putting npt_umbrella.mdp,md_umbrella.mdp,conf140.gro(used for
npt_umbrella), npt140.gro,md_umbrella run video in the following link:
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0


Am I still missing some drastic steps ? Please suggest me if I do. I'm
totally lost here in this regard.



Again, don't restrain the protein.  I've said this multiple times.

The pull setup looks reasonable.  Maybe you just need a stronger force
constant, or you should not use the COM of the whole protein, instead the
COM of a few important residues (use an index group with gmx traj -ox -com
to get its coordinates).  If the specified vector is off, so too will be
the resulting biasing 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

==
--
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 

Re: [gmx-users] ligand moving out during umbrella sampling

[abhisek Mondal]

This time I think I got ligand restrained successfully during the umbrella
sampling. I have removed the restrain from protein, as per your advice.
Defined the COM vector in md_umbrella.mdp, applied pull_k1=1000 and used
pull_rate1=0.0.
I have uploaded the trajectory movie (and other mdp files) in the following
link:
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

However, I'm facing a problem. Due to the withdrawal of the position
restrain of protein. The protein and ligand (together) is moving around the
box and resulting in "Distance of pull group 1 (10.441990 nm) is larger
than 0.49 times the box size (10.646989)" error.

As per the video I have uploaded, if I assume this approach worked, then
how can I avoid this error ? Is  there any way to make sure the
protein-ligand remains in the middle of the box (or nearby). I have taken
pretty large box compared to the protein structure from the beginning.

Please suggest me a way out.

On Mon, May 15, 2017 at 5:48 PM, Justin Lemkul  wrote:

>
>
> On 5/15/17 2:45 AM, abhisek Mondal wrote:
>
>> On Thu, May 11, 2017 at 9:03 PM, Justin Lemkul  wrote:
>>
>>
>>>
>>> On 5/11/17 9:21 AM, abhisek Mondal wrote:
>>>
>>> On Thu, May 11, 2017 at 11:02 AM, abhisek Mondal 
 wrote:

 Hi,

>
> Thank you for the explanation. It really cleared some concepts. But I'm
> still having my ligand moving in this step. I have modified the code
> as:
> ; Pull code
> pull= umbrella
> pull_ngroups= 1
> pull_group0 = Protein_chain_A
> pull_group1 = ACO
> pull_geometry   = direction ; simple distance increase
> pull_dim   = Y Y Y ; not to allow ligand move along
> other
> dir
> pull_rate1 = 0.0
> pull_k1   = 1000   ; kJ mol^-1 nm^-2
> pull_start   = yes   ; define initial COM distance > 0
> pull_vec1   = 0 0 -1
>
>
> Note that with "direction" geometry, only pull_vec1 is acting.
>>> pull_dim
>>> is ignored.
>>>
>>> The ligand was previously moving along x,y direction when I was using
>>>
 pull_dim  = N N Y. So I changed it to Y in all direction and provided 0
> as
> vector  and pull_rate1=0.0, so that it does not move much. But at the
> end
> of a 10ns run, I see that the ligand is still moving as it was earlier.
>
> It shows me:
>
  Pull group  natoms  pbc atom  distance at start reference at t=0
0  1132936665
159  1618  -1.555-1.555
 Is it ok withe negative value ? Anyway this setup is not working.


 Again you're trying to just apply the restraint to one dimension and it
>>> looks to be fairly arbitrary.  I already suggested using the vector
>>> connecting the ligand COM with the binding site residues' COM and using
>>> that as pull_vec1.  Draw it out.  It makes a lot more sense than trying
>>> to
>>> restrain only along one axis, which as I have said before, makes no sense
>>> in this case.
>>>
>>> Thank you for such detailed suggestion.
>>>
>> I followed on as per your suggestion. Calculated COM of protein and
>> Ligand.
>> Calculated protein-lig vector (using COM) to be used for pulling (as
>> pull_vec1).
>> Pulling also achieved successfully.
>> But after pulling, when I performed the brief npt_umbrella run with
>> pull_rate1=0, I found the ligand is moving little bit. Could not
>> understand
>> what I have mistaken this time.
>> So I moved on for umbrella sampling mdrun step, with pull_rate1=0 and
>> pull_vec1=as determined from COM calculations. Despite I found that the
>> ligand is moving vigorously and got pulled away probably.
>> I'm putting npt_umbrella.mdp,md_umbrella.mdp,conf140.gro(used for
>> npt_umbrella), npt140.gro,md_umbrella run video in the following link:
>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>>
>>
>> Am I still missing some drastic steps ? Please suggest me if I do. I'm
>> totally lost here in this regard.
>>
>>
> Again, don't restrain the protein.  I've said this multiple times.
>
> The pull setup looks reasonable.  Maybe you just need a stronger force
> constant, or you should not use the COM of the whole protein, instead the
> COM of a few important residues (use an index group with gmx traj -ox -com
> to get its coordinates).  If the specified vector is off, so too will be
> the resulting biasing 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
> 

Re: [gmx-users] ligand moving out during umbrella sampling

[Justin Lemkul]

On 5/15/17 2:45 AM, abhisek Mondal wrote:

On Thu, May 11, 2017 at 9:03 PM, Justin Lemkul  wrote:




On 5/11/17 9:21 AM, abhisek Mondal wrote:


On Thu, May 11, 2017 at 11:02 AM, abhisek Mondal 
wrote:

Hi,


Thank you for the explanation. It really cleared some concepts. But I'm
still having my ligand moving in this step. I have modified the code as:
; Pull code
pull= umbrella
pull_ngroups= 1
pull_group0 = Protein_chain_A
pull_group1 = ACO
pull_geometry   = direction ; simple distance increase
pull_dim   = Y Y Y ; not to allow ligand move along other
dir
pull_rate1 = 0.0
pull_k1   = 1000   ; kJ mol^-1 nm^-2
pull_start   = yes   ; define initial COM distance > 0
pull_vec1   = 0 0 -1



Note that with "direction" geometry, only pull_vec1 is acting.  pull_dim
is ignored.

The ligand was previously moving along x,y direction when I was using

pull_dim  = N N Y. So I changed it to Y in all direction and provided 0
as
vector  and pull_rate1=0.0, so that it does not move much. But at the end
of a 10ns run, I see that the ligand is still moving as it was earlier.

It shows me:

 Pull group  natoms  pbc atom  distance at start reference at t=0
   0  1132936665
   159  1618  -1.555-1.555
Is it ok withe negative value ? Anyway this setup is not working.



Again you're trying to just apply the restraint to one dimension and it
looks to be fairly arbitrary.  I already suggested using the vector
connecting the ligand COM with the binding site residues' COM and using
that as pull_vec1.  Draw it out.  It makes a lot more sense than trying to
restrain only along one axis, which as I have said before, makes no sense
in this case.

Thank you for such detailed suggestion.

I followed on as per your suggestion. Calculated COM of protein and Ligand.
Calculated protein-lig vector (using COM) to be used for pulling (as
pull_vec1).
Pulling also achieved successfully.
But after pulling, when I performed the brief npt_umbrella run with
pull_rate1=0, I found the ligand is moving little bit. Could not understand
what I have mistaken this time.
So I moved on for umbrella sampling mdrun step, with pull_rate1=0 and
pull_vec1=as determined from COM calculations. Despite I found that the
ligand is moving vigorously and got pulled away probably.
I'm putting npt_umbrella.mdp,md_umbrella.mdp,conf140.gro(used for
npt_umbrella), npt140.gro,md_umbrella run video in the following link:
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0


Am I still missing some drastic steps ? Please suggest me if I do. I'm
totally lost here in this regard.



Again, don't restrain the protein.  I've said this multiple times.

The pull setup looks reasonable.  Maybe you just need a stronger force constant, 
or you should not use the COM of the whole protein, instead the COM of a few 
important residues (use an index group with gmx traj -ox -com to get its 
coordinates).  If the specified vector is off, so too will be the resulting 
biasing 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

==
--
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.

Re: [gmx-users] ligand moving out during umbrella sampling

[abhisek Mondal]

On Thu, May 11, 2017 at 9:03 PM, Justin Lemkul  wrote:

>
>
> On 5/11/17 9:21 AM, abhisek Mondal wrote:
>
>> On Thu, May 11, 2017 at 11:02 AM, abhisek Mondal 
>> wrote:
>>
>> Hi,
>>>
>>> Thank you for the explanation. It really cleared some concepts. But I'm
>>> still having my ligand moving in this step. I have modified the code as:
>>> ; Pull code
>>> pull= umbrella
>>> pull_ngroups= 1
>>> pull_group0 = Protein_chain_A
>>> pull_group1 = ACO
>>> pull_geometry   = direction ; simple distance increase
>>> pull_dim   = Y Y Y ; not to allow ligand move along other
>>> dir
>>> pull_rate1 = 0.0
>>> pull_k1   = 1000   ; kJ mol^-1 nm^-2
>>> pull_start   = yes   ; define initial COM distance > 0
>>> pull_vec1   = 0 0 -1
>>>
>>>
> Note that with "direction" geometry, only pull_vec1 is acting.  pull_dim
> is ignored.
>
> The ligand was previously moving along x,y direction when I was using
>>> pull_dim  = N N Y. So I changed it to Y in all direction and provided 0
>>> as
>>> vector  and pull_rate1=0.0, so that it does not move much. But at the end
>>> of a 10ns run, I see that the ligand is still moving as it was earlier.
>>>
>>> It shows me:
>>  Pull group  natoms  pbc atom  distance at start reference at t=0
>>0  1132936665
>>159  1618  -1.555-1.555
>> Is it ok withe negative value ? Anyway this setup is not working.
>>
>>
> Again you're trying to just apply the restraint to one dimension and it
> looks to be fairly arbitrary.  I already suggested using the vector
> connecting the ligand COM with the binding site residues' COM and using
> that as pull_vec1.  Draw it out.  It makes a lot more sense than trying to
> restrain only along one axis, which as I have said before, makes no sense
> in this case.
>
> Thank you for such detailed suggestion.
I followed on as per your suggestion. Calculated COM of protein and Ligand.
Calculated protein-lig vector (using COM) to be used for pulling (as
pull_vec1).
Pulling also achieved successfully.
But after pulling, when I performed the brief npt_umbrella run with
pull_rate1=0, I found the ligand is moving little bit. Could not understand
what I have mistaken this time.
So I moved on for umbrella sampling mdrun step, with pull_rate1=0 and
pull_vec1=as determined from COM calculations. Despite I found that the
ligand is moving vigorously and got pulled away probably.
I'm putting npt_umbrella.mdp,md_umbrella.mdp,conf140.gro(used for
npt_umbrella), npt140.gro,md_umbrella run video in the following link:
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0


Am I still missing some drastic steps ? Please suggest me if I do. I'm
totally lost here in this regard.





> -Justin
>
>
>>> I have choose my reaction coordinate to be along -Z axis and want to
>>> apply
>>> biasing potential accordingly with restraining the ligand movement. Can
>>> you
>>> please suggest where am I failing with this code ?
>>>
>>> Thank you.
>>>
>>>
>>>
>>> On Tue, May 9, 2017 at 1:11 AM, Justin Lemkul  wrote:
>>>
>>>

 On 5/8/17 10:00 AM, abhisek Mondal wrote:

 On Sun, May 7, 2017 at 11:37 PM, Justin Lemkul  wrote:
>
>
>
>> On 5/7/17 1:57 AM, abhisek Mondal wrote:
>>
>> Hi,
>>
>>>
>>> For your ease of understanding regarding what is happening during
>>> this
>>> above said umbrella-mdrun, I have shared the trajectory video file
>>> the
>>> following link.
>>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>>>
>>> Is this normal given that the mdp code being used ? I basically have
>>> no
>>> idea with this step, so please help me out. I'm using gromacs-4.6.2.
>>>
>>>
>>> Your setup is incorrect.  You're applying a biasing potential only
>>>
>> along
>> z, so the ligand can move freely along x and y.  A protein-ligand
>> complex
>> has spherical symmetry, so you should set the reaction coordinate to
>> the
>> vector connecting the ligand with some suitable subset of interacting
>> protein residues.
>>
>>
>
> I don't get it.
> We are trying not to move our configuration (generated after pulling
> simulation) along the reaction coordinate, so for restraining we are
> supposed to set pull_rate1=0.0.
>
>
 Of course.  But you said set pull_k = 0 which does not make sense.  The
 pulling rate *is* zero during umbrella sampling (no net displacement,
 restrain to the specified distance along the reaction coordinate) and
 pulling force constant should be non-zero.

 If applying biasing potential only along z is causing movement along x
 and

> y then what if we apply the biasing potential along x,y,z ? Will it
> cause

Re: [gmx-users] ligand moving out during umbrella sampling

[abhisek Mondal]

On Thu, May 11, 2017 at 9:03 PM, Justin Lemkul  wrote:

>
>
> On 5/11/17 9:21 AM, abhisek Mondal wrote:
>
>> On Thu, May 11, 2017 at 11:02 AM, abhisek Mondal 
>> wrote:
>>
>> Hi,
>>>
>>> Thank you for the explanation. It really cleared some concepts. But I'm
>>> still having my ligand moving in this step. I have modified the code as:
>>> ; Pull code
>>> pull= umbrella
>>> pull_ngroups= 1
>>> pull_group0 = Protein_chain_A
>>> pull_group1 = ACO
>>> pull_geometry   = direction ; simple distance increase
>>> pull_dim   = Y Y Y ; not to allow ligand move along other
>>> dir
>>> pull_rate1 = 0.0
>>> pull_k1   = 1000   ; kJ mol^-1 nm^-2
>>> pull_start   = yes   ; define initial COM distance > 0
>>> pull_vec1   = 0 0 -1
>>>
>>>
> Note that with "direction" geometry, only pull_vec1 is acting.  pull_dim
> is ignored.
>
> The ligand was previously moving along x,y direction when I was using
>>> pull_dim  = N N Y. So I changed it to Y in all direction and provided 0
>>> as
>>> vector  and pull_rate1=0.0, so that it does not move much. But at the end
>>> of a 10ns run, I see that the ligand is still moving as it was earlier.
>>>
>>> It shows me:
>>  Pull group  natoms  pbc atom  distance at start reference at t=0
>>0  1132936665
>>159  1618  -1.555-1.555
>> Is it ok withe negative value ? Anyway this setup is not working.
>>
>>
> Again you're trying to just apply the restraint to one dimension and it
> looks to be fairly arbitrary.  I already suggested using the vector
> connecting the ligand COM with the binding site residues' COM and using
> that as pull_vec1.  Draw it out.  It makes a lot more sense than trying to
> restrain only along one axis, which as I have said before, makes no sense
> in this case.


As to obtain COM of ligand I'm using:  "g_traj_mpi -ox aco_com -com -s
npt.tpr" and taking the last frame's xy,z coordinate from the .xvg file
generated from that command.
 394 14.1362 14.4649 5.94131
 395 14.1435 14.45 5.94041
 396 14.0858 14.4461 5.90442
 397 14.1398 14.4164 5.86902
 398 14.1514 14.4434 5.8461
 399 14.1344 14.421 5.88976
 400 14.1996 14.4613 5.82814

Is this approach correct for taking COM?

Another question is that, how can I calculate COM for specific set of
residues ? If the above approach (for calculating Ligand COM) is correct
then it allows calculation of COM for whole protein only.
Please do suggest a way.



Thank you.



>
> -Justin
>
>
>>>
-- 
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Re: [gmx-users] ligand moving out during umbrella sampling

[Justin Lemkul]

On 5/11/17 1:25 PM, abhisek Mondal wrote:

Alright. I'm trying as per your advice. Actually my system is pretty big
and due to constraint of computation power it is taking me more time to
test vector setup. I really appreciate your time. Thanks a lot for your
suggestions.

One thing I'm worried about here. In previous mail, I mentioned the
"distance at start" and "ref at t=0" is negative. What does the negative
value signify, I mean how can distance be negative ? Is is due to my poorly
given vector definition or something else ?



It's a vector quantity.  It can be positive or negative depending on how you 
define the groups and what their positions are.  And you're telling grompp to 
pull along the negative-z dimension.


-Justin


On Thu, May 11, 2017 at 9:03 PM, Justin Lemkul  wrote:




On 5/11/17 9:21 AM, abhisek Mondal wrote:


On Thu, May 11, 2017 at 11:02 AM, abhisek Mondal 
wrote:

Hi,


Thank you for the explanation. It really cleared some concepts. But I'm
still having my ligand moving in this step. I have modified the code as:
; Pull code
pull= umbrella
pull_ngroups= 1
pull_group0 = Protein_chain_A
pull_group1 = ACO
pull_geometry   = direction ; simple distance increase
pull_dim   = Y Y Y ; not to allow ligand move along other
dir
pull_rate1 = 0.0
pull_k1   = 1000   ; kJ mol^-1 nm^-2
pull_start   = yes   ; define initial COM distance > 0
pull_vec1   = 0 0 -1



Note that with "direction" geometry, only pull_vec1 is acting.  pull_dim
is ignored.

The ligand was previously moving along x,y direction when I was using

pull_dim  = N N Y. So I changed it to Y in all direction and provided 0
as
vector  and pull_rate1=0.0, so that it does not move much. But at the end
of a 10ns run, I see that the ligand is still moving as it was earlier.

It shows me:

 Pull group  natoms  pbc atom  distance at start reference at t=0
   0  1132936665
   159  1618  -1.555-1.555
Is it ok withe negative value ? Anyway this setup is not working.



Again you're trying to just apply the restraint to one dimension and it
looks to be fairly arbitrary.  I already suggested using the vector
connecting the ligand COM with the binding site residues' COM and using
that as pull_vec1.  Draw it out.  It makes a lot more sense than trying to
restrain only along one axis, which as I have said before, makes no sense
in this case.

-Justin



I have choose my reaction coordinate to be along -Z axis and want to
apply
biasing potential accordingly with restraining the ligand movement. Can
you
please suggest where am I failing with this code ?

Thank you.



On Tue, May 9, 2017 at 1:11 AM, Justin Lemkul  wrote:




On 5/8/17 10:00 AM, abhisek Mondal wrote:

On Sun, May 7, 2017 at 11:37 PM, Justin Lemkul  wrote:





On 5/7/17 1:57 AM, abhisek Mondal wrote:

Hi,



For your ease of understanding regarding what is happening during
this
above said umbrella-mdrun, I have shared the trajectory video file
the
following link.
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

Is this normal given that the mdp code being used ? I basically have
no
idea with this step, so please help me out. I'm using gromacs-4.6.2.


Your setup is incorrect.  You're applying a biasing potential only


along
z, so the ligand can move freely along x and y.  A protein-ligand
complex
has spherical symmetry, so you should set the reaction coordinate to
the
vector connecting the ligand with some suitable subset of interacting
protein residues.




I don't get it.
We are trying not to move our configuration (generated after pulling
simulation) along the reaction coordinate, so for restraining we are
supposed to set pull_rate1=0.0.



Of course.  But you said set pull_k = 0 which does not make sense.  The
pulling rate *is* zero during umbrella sampling (no net displacement,
restrain to the specified distance along the reaction coordinate) and
pulling force constant should be non-zero.

If applying biasing potential only along z is causing movement along x
and


y then what if we apply the biasing potential along x,y,z ? Will it
cause
any good in restraining the ligand?


This is how it should be done.  The reaction coordinate should be

suitably defined based on the geometry of the system.  As I suggested
before, choose some representative residues in the active site as one
group
and the ligand as the other.  Thus defines the reaction coordinate
without
any presupposition of anything being aligned with a Cartesian axis,
which
is rarely the case.

Moreover, you said previously "A protein-ligand complex has spherical


symmetry, so you should set the reaction coordinate to the vector
connecting the ligand with some suitable subset of interacting protein
residues.". It is really unclear to me, could you 

Re: [gmx-users] ligand moving out during umbrella sampling

[abhisek Mondal]

Alright. I'm trying as per your advice. Actually my system is pretty big
and due to constraint of computation power it is taking me more time to
test vector setup. I really appreciate your time. Thanks a lot for your
suggestions.

One thing I'm worried about here. In previous mail, I mentioned the
"distance at start" and "ref at t=0" is negative. What does the negative
value signify, I mean how can distance be negative ? Is is due to my poorly
given vector definition or something else ?

On Thu, May 11, 2017 at 9:03 PM, Justin Lemkul  wrote:

>
>
> On 5/11/17 9:21 AM, abhisek Mondal wrote:
>
>> On Thu, May 11, 2017 at 11:02 AM, abhisek Mondal 
>> wrote:
>>
>> Hi,
>>>
>>> Thank you for the explanation. It really cleared some concepts. But I'm
>>> still having my ligand moving in this step. I have modified the code as:
>>> ; Pull code
>>> pull= umbrella
>>> pull_ngroups= 1
>>> pull_group0 = Protein_chain_A
>>> pull_group1 = ACO
>>> pull_geometry   = direction ; simple distance increase
>>> pull_dim   = Y Y Y ; not to allow ligand move along other
>>> dir
>>> pull_rate1 = 0.0
>>> pull_k1   = 1000   ; kJ mol^-1 nm^-2
>>> pull_start   = yes   ; define initial COM distance > 0
>>> pull_vec1   = 0 0 -1
>>>
>>>
> Note that with "direction" geometry, only pull_vec1 is acting.  pull_dim
> is ignored.
>
> The ligand was previously moving along x,y direction when I was using
>>> pull_dim  = N N Y. So I changed it to Y in all direction and provided 0
>>> as
>>> vector  and pull_rate1=0.0, so that it does not move much. But at the end
>>> of a 10ns run, I see that the ligand is still moving as it was earlier.
>>>
>>> It shows me:
>>  Pull group  natoms  pbc atom  distance at start reference at t=0
>>0  1132936665
>>159  1618  -1.555-1.555
>> Is it ok withe negative value ? Anyway this setup is not working.
>>
>>
> Again you're trying to just apply the restraint to one dimension and it
> looks to be fairly arbitrary.  I already suggested using the vector
> connecting the ligand COM with the binding site residues' COM and using
> that as pull_vec1.  Draw it out.  It makes a lot more sense than trying to
> restrain only along one axis, which as I have said before, makes no sense
> in this case.
>
> -Justin
>
>
>>> I have choose my reaction coordinate to be along -Z axis and want to
>>> apply
>>> biasing potential accordingly with restraining the ligand movement. Can
>>> you
>>> please suggest where am I failing with this code ?
>>>
>>> Thank you.
>>>
>>>
>>>
>>> On Tue, May 9, 2017 at 1:11 AM, Justin Lemkul  wrote:
>>>
>>>

 On 5/8/17 10:00 AM, abhisek Mondal wrote:

 On Sun, May 7, 2017 at 11:37 PM, Justin Lemkul  wrote:
>
>
>
>> On 5/7/17 1:57 AM, abhisek Mondal wrote:
>>
>> Hi,
>>
>>>
>>> For your ease of understanding regarding what is happening during
>>> this
>>> above said umbrella-mdrun, I have shared the trajectory video file
>>> the
>>> following link.
>>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>>>
>>> Is this normal given that the mdp code being used ? I basically have
>>> no
>>> idea with this step, so please help me out. I'm using gromacs-4.6.2.
>>>
>>>
>>> Your setup is incorrect.  You're applying a biasing potential only
>>>
>> along
>> z, so the ligand can move freely along x and y.  A protein-ligand
>> complex
>> has spherical symmetry, so you should set the reaction coordinate to
>> the
>> vector connecting the ligand with some suitable subset of interacting
>> protein residues.
>>
>>
>
> I don't get it.
> We are trying not to move our configuration (generated after pulling
> simulation) along the reaction coordinate, so for restraining we are
> supposed to set pull_rate1=0.0.
>
>
 Of course.  But you said set pull_k = 0 which does not make sense.  The
 pulling rate *is* zero during umbrella sampling (no net displacement,
 restrain to the specified distance along the reaction coordinate) and
 pulling force constant should be non-zero.

 If applying biasing potential only along z is causing movement along x
 and

> y then what if we apply the biasing potential along x,y,z ? Will it
> cause
> any good in restraining the ligand?
>
>
> This is how it should be done.  The reaction coordinate should be
 suitably defined based on the geometry of the system.  As I suggested
 before, choose some representative residues in the active site as one
 group
 and the ligand as the other.  Thus defines the reaction coordinate
 without
 any presupposition of anything being aligned with a 

Re: [gmx-users] ligand moving out during umbrella sampling

[Justin Lemkul]

On 5/11/17 9:21 AM, abhisek Mondal wrote:

On Thu, May 11, 2017 at 11:02 AM, abhisek Mondal 
wrote:


Hi,

Thank you for the explanation. It really cleared some concepts. But I'm
still having my ligand moving in this step. I have modified the code as:
; Pull code
pull= umbrella
pull_ngroups= 1
pull_group0 = Protein_chain_A
pull_group1 = ACO
pull_geometry   = direction ; simple distance increase
pull_dim   = Y Y Y ; not to allow ligand move along other
dir
pull_rate1 = 0.0
pull_k1   = 1000   ; kJ mol^-1 nm^-2
pull_start   = yes   ; define initial COM distance > 0
pull_vec1   = 0 0 -1



Note that with "direction" geometry, only pull_vec1 is acting.  pull_dim is 
ignored.


The ligand was previously moving along x,y direction when I was using
pull_dim  = N N Y. So I changed it to Y in all direction and provided 0 as
vector  and pull_rate1=0.0, so that it does not move much. But at the end
of a 10ns run, I see that the ligand is still moving as it was earlier.


It shows me:
 Pull group  natoms  pbc atom  distance at start reference at t=0
   0  1132936665
   159  1618  -1.555-1.555
Is it ok withe negative value ? Anyway this setup is not working.



Again you're trying to just apply the restraint to one dimension and it looks to 
be fairly arbitrary.  I already suggested using the vector connecting the ligand 
COM with the binding site residues' COM and using that as pull_vec1.  Draw it 
out.  It makes a lot more sense than trying to restrain only along one axis, 
which as I have said before, makes no sense in this case.


-Justin



I have choose my reaction coordinate to be along -Z axis and want to apply
biasing potential accordingly with restraining the ligand movement. Can you
please suggest where am I failing with this code ?

Thank you.



On Tue, May 9, 2017 at 1:11 AM, Justin Lemkul  wrote:




On 5/8/17 10:00 AM, abhisek Mondal wrote:


On Sun, May 7, 2017 at 11:37 PM, Justin Lemkul  wrote:




On 5/7/17 1:57 AM, abhisek Mondal wrote:

Hi,


For your ease of understanding regarding what is happening during this
above said umbrella-mdrun, I have shared the trajectory video file the
following link.
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

Is this normal given that the mdp code being used ? I basically have no
idea with this step, so please help me out. I'm using gromacs-4.6.2.


Your setup is incorrect.  You're applying a biasing potential only

along
z, so the ligand can move freely along x and y.  A protein-ligand
complex
has spherical symmetry, so you should set the reaction coordinate to the
vector connecting the ligand with some suitable subset of interacting
protein residues.




I don't get it.
We are trying not to move our configuration (generated after pulling
simulation) along the reaction coordinate, so for restraining we are
supposed to set pull_rate1=0.0.



Of course.  But you said set pull_k = 0 which does not make sense.  The
pulling rate *is* zero during umbrella sampling (no net displacement,
restrain to the specified distance along the reaction coordinate) and
pulling force constant should be non-zero.

If applying biasing potential only along z is causing movement along x and

y then what if we apply the biasing potential along x,y,z ? Will it cause
any good in restraining the ligand?



This is how it should be done.  The reaction coordinate should be
suitably defined based on the geometry of the system.  As I suggested
before, choose some representative residues in the active site as one group
and the ligand as the other.  Thus defines the reaction coordinate without
any presupposition of anything being aligned with a Cartesian axis, which
is rarely the case.

Moreover, you said previously "A protein-ligand complex has spherical

symmetry, so you should set the reaction coordinate to the vector
connecting the ligand with some suitable subset of interacting protein
residues.". It is really unclear to me, could you please give me some
examples to understand it more simply? I had pulled the ligand along -z
axis, doesn't it mean that the reaction coordinate is to be that way ?
The
fact that I'm struggling with is to restrain the pull configurations for
further sampling.



The reaction coordinate is whatever you define it to be.  Whether or not
pulling along the z-axis makes sense depends on the orientation of the
system and the intrinsic geometry.  In your case, it doesn't make sense.
In my case (the tutorial, the unidirectional growth of an amyloid fibril)
it does make sense to use a single Cartesian axis for the SMD portion and
subsequent umbrella sampling.

I'm really a beginner, so maybe I'm asking stupid questions. Please give

me
some advise. I'm really unable to decipher the scenario in comparison to
your amyloid 

Re: [gmx-users] ligand moving out during umbrella sampling

[abhisek Mondal]

On Thu, May 11, 2017 at 11:02 AM, abhisek Mondal 
wrote:

> Hi,
>
> Thank you for the explanation. It really cleared some concepts. But I'm
> still having my ligand moving in this step. I have modified the code as:
> ; Pull code
> pull= umbrella
> pull_ngroups= 1
> pull_group0 = Protein_chain_A
> pull_group1 = ACO
> pull_geometry   = direction ; simple distance increase
> pull_dim   = Y Y Y ; not to allow ligand move along other
> dir
> pull_rate1 = 0.0
> pull_k1   = 1000   ; kJ mol^-1 nm^-2
> pull_start   = yes   ; define initial COM distance > 0
> pull_vec1   = 0 0 -1
>
> The ligand was previously moving along x,y direction when I was using
> pull_dim  = N N Y. So I changed it to Y in all direction and provided 0 as
> vector  and pull_rate1=0.0, so that it does not move much. But at the end
> of a 10ns run, I see that the ligand is still moving as it was earlier.
>
It shows me:
 Pull group  natoms  pbc atom  distance at start reference at t=0
   0  1132936665
   159  1618  -1.555-1.555
Is it ok withe negative value ? Anyway this setup is not working.

>
> I have choose my reaction coordinate to be along -Z axis and want to apply
> biasing potential accordingly with restraining the ligand movement. Can you
> please suggest where am I failing with this code ?
>
> Thank you.
>
>
>
> On Tue, May 9, 2017 at 1:11 AM, Justin Lemkul  wrote:
>
>>
>>
>> On 5/8/17 10:00 AM, abhisek Mondal wrote:
>>
>>> On Sun, May 7, 2017 at 11:37 PM, Justin Lemkul  wrote:
>>>
>>>

 On 5/7/17 1:57 AM, abhisek Mondal wrote:

 Hi,
>
> For your ease of understanding regarding what is happening during this
> above said umbrella-mdrun, I have shared the trajectory video file the
> following link.
> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>
> Is this normal given that the mdp code being used ? I basically have no
> idea with this step, so please help me out. I'm using gromacs-4.6.2.
>
>
> Your setup is incorrect.  You're applying a biasing potential only
 along
 z, so the ligand can move freely along x and y.  A protein-ligand
 complex
 has spherical symmetry, so you should set the reaction coordinate to the
 vector connecting the ligand with some suitable subset of interacting
 protein residues.

>>>
>>>
>>> I don't get it.
>>> We are trying not to move our configuration (generated after pulling
>>> simulation) along the reaction coordinate, so for restraining we are
>>> supposed to set pull_rate1=0.0.
>>>
>>
>> Of course.  But you said set pull_k = 0 which does not make sense.  The
>> pulling rate *is* zero during umbrella sampling (no net displacement,
>> restrain to the specified distance along the reaction coordinate) and
>> pulling force constant should be non-zero.
>>
>> If applying biasing potential only along z is causing movement along x and
>>> y then what if we apply the biasing potential along x,y,z ? Will it cause
>>> any good in restraining the ligand?
>>>
>>>
>> This is how it should be done.  The reaction coordinate should be
>> suitably defined based on the geometry of the system.  As I suggested
>> before, choose some representative residues in the active site as one group
>> and the ligand as the other.  Thus defines the reaction coordinate without
>> any presupposition of anything being aligned with a Cartesian axis, which
>> is rarely the case.
>>
>> Moreover, you said previously "A protein-ligand complex has spherical
>>> symmetry, so you should set the reaction coordinate to the vector
>>> connecting the ligand with some suitable subset of interacting protein
>>> residues.". It is really unclear to me, could you please give me some
>>> examples to understand it more simply? I had pulled the ligand along -z
>>> axis, doesn't it mean that the reaction coordinate is to be that way ?
>>> The
>>> fact that I'm struggling with is to restrain the pull configurations for
>>> further sampling.
>>>
>>>
>> The reaction coordinate is whatever you define it to be.  Whether or not
>> pulling along the z-axis makes sense depends on the orientation of the
>> system and the intrinsic geometry.  In your case, it doesn't make sense.
>> In my case (the tutorial, the unidirectional growth of an amyloid fibril)
>> it does make sense to use a single Cartesian axis for the SMD portion and
>> subsequent umbrella sampling.
>>
>> I'm really a beginner, so maybe I'm asking stupid questions. Please give
>>> me
>>> some advise. I'm really unable to decipher the scenario in comparison to
>>> your amyloid article in JPCB.
>>>
>>>
>> You should read the article to understand why I did what I did in the
>> tutorial, and then move on to reading articles that are more similar to
>> your case.  These will 

Re: [gmx-users] ligand moving out during umbrella sampling

[abhisek Mondal]

Hi,

Thank you for the explanation. It really cleared some concepts. But I'm
still having my ligand moving in this step. I have modified the code as:
; Pull code
pull= umbrella
pull_ngroups= 1
pull_group0 = Protein_chain_A
pull_group1 = ACO
pull_geometry   = direction ; simple distance increase
pull_dim   = Y Y Y ; not to allow ligand move along other
dir
pull_rate1 = 0.0
pull_k1   = 1000   ; kJ mol^-1 nm^-2
pull_start   = yes   ; define initial COM distance > 0
pull_vec1   = 0 0 -1

The ligand was previously moving along x,y direction when I was using
pull_dim  = N N Y. So I changed it to Y in all direction and provided 0 as
vector  and pull_rate1=0.0, so that it does not move much. But at the end
of a 10ns run, I see that the ligand is still moving as it was earlier.

I have choose my reaction coordinate to be along -Z axis and want to apply
biasing potential accordingly with restraining the ligand movement. Can you
please suggest where am I failing with this code ?

Thank you.



On Tue, May 9, 2017 at 1:11 AM, Justin Lemkul  wrote:

>
>
> On 5/8/17 10:00 AM, abhisek Mondal wrote:
>
>> On Sun, May 7, 2017 at 11:37 PM, Justin Lemkul  wrote:
>>
>>
>>>
>>> On 5/7/17 1:57 AM, abhisek Mondal wrote:
>>>
>>> Hi,

 For your ease of understanding regarding what is happening during this
 above said umbrella-mdrun, I have shared the trajectory video file the
 following link.
 https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

 Is this normal given that the mdp code being used ? I basically have no
 idea with this step, so please help me out. I'm using gromacs-4.6.2.


 Your setup is incorrect.  You're applying a biasing potential only along
>>> z, so the ligand can move freely along x and y.  A protein-ligand complex
>>> has spherical symmetry, so you should set the reaction coordinate to the
>>> vector connecting the ligand with some suitable subset of interacting
>>> protein residues.
>>>
>>
>>
>> I don't get it.
>> We are trying not to move our configuration (generated after pulling
>> simulation) along the reaction coordinate, so for restraining we are
>> supposed to set pull_rate1=0.0.
>>
>
> Of course.  But you said set pull_k = 0 which does not make sense.  The
> pulling rate *is* zero during umbrella sampling (no net displacement,
> restrain to the specified distance along the reaction coordinate) and
> pulling force constant should be non-zero.
>
> If applying biasing potential only along z is causing movement along x and
>> y then what if we apply the biasing potential along x,y,z ? Will it cause
>> any good in restraining the ligand?
>>
>>
> This is how it should be done.  The reaction coordinate should be suitably
> defined based on the geometry of the system.  As I suggested before, choose
> some representative residues in the active site as one group and the ligand
> as the other.  Thus defines the reaction coordinate without any
> presupposition of anything being aligned with a Cartesian axis, which is
> rarely the case.
>
> Moreover, you said previously "A protein-ligand complex has spherical
>> symmetry, so you should set the reaction coordinate to the vector
>> connecting the ligand with some suitable subset of interacting protein
>> residues.". It is really unclear to me, could you please give me some
>> examples to understand it more simply? I had pulled the ligand along -z
>> axis, doesn't it mean that the reaction coordinate is to be that way ? The
>> fact that I'm struggling with is to restrain the pull configurations for
>> further sampling.
>>
>>
> The reaction coordinate is whatever you define it to be.  Whether or not
> pulling along the z-axis makes sense depends on the orientation of the
> system and the intrinsic geometry.  In your case, it doesn't make sense.
> In my case (the tutorial, the unidirectional growth of an amyloid fibril)
> it does make sense to use a single Cartesian axis for the SMD portion and
> subsequent umbrella sampling.
>
> I'm really a beginner, so maybe I'm asking stupid questions. Please give me
>> some advise. I'm really unable to decipher the scenario in comparison to
>> your amyloid article in JPCB.
>>
>>
> You should read the article to understand why I did what I did in the
> tutorial, and then move on to reading articles that are more similar to
> your case.  These will be much more relevant to what you're doing.
>
> -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
>
> 

Re: [gmx-users] ligand moving out during umbrella sampling

[Justin Lemkul]

On 5/8/17 10:00 AM, abhisek Mondal wrote:

On Sun, May 7, 2017 at 11:37 PM, Justin Lemkul  wrote:




On 5/7/17 1:57 AM, abhisek Mondal wrote:


Hi,

For your ease of understanding regarding what is happening during this
above said umbrella-mdrun, I have shared the trajectory video file the
following link.
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

Is this normal given that the mdp code being used ? I basically have no
idea with this step, so please help me out. I'm using gromacs-4.6.2.



Your setup is incorrect.  You're applying a biasing potential only along
z, so the ligand can move freely along x and y.  A protein-ligand complex
has spherical symmetry, so you should set the reaction coordinate to the
vector connecting the ligand with some suitable subset of interacting
protein residues.



I don't get it.
We are trying not to move our configuration (generated after pulling
simulation) along the reaction coordinate, so for restraining we are
supposed to set pull_rate1=0.0.


Of course.  But you said set pull_k = 0 which does not make sense.  The pulling 
rate *is* zero during umbrella sampling (no net displacement, restrain to the 
specified distance along the reaction coordinate) and pulling force constant 
should be non-zero.



If applying biasing potential only along z is causing movement along x and
y then what if we apply the biasing potential along x,y,z ? Will it cause
any good in restraining the ligand?



This is how it should be done.  The reaction coordinate should be suitably 
defined based on the geometry of the system.  As I suggested before, choose some 
representative residues in the active site as one group and the ligand as the 
other.  Thus defines the reaction coordinate without any presupposition of 
anything being aligned with a Cartesian axis, which is rarely the case.



Moreover, you said previously "A protein-ligand complex has spherical
symmetry, so you should set the reaction coordinate to the vector
connecting the ligand with some suitable subset of interacting protein
residues.". It is really unclear to me, could you please give me some
examples to understand it more simply? I had pulled the ligand along -z
axis, doesn't it mean that the reaction coordinate is to be that way ? The
fact that I'm struggling with is to restrain the pull configurations for
further sampling.



The reaction coordinate is whatever you define it to be.  Whether or not pulling 
along the z-axis makes sense depends on the orientation of the system and the 
intrinsic geometry.  In your case, it doesn't make sense.  In my case (the 
tutorial, the unidirectional growth of an amyloid fibril) it does make sense to 
use a single Cartesian axis for the SMD portion and subsequent umbrella sampling.



I'm really a beginner, so maybe I'm asking stupid questions. Please give me
some advise. I'm really unable to decipher the scenario in comparison to
your amyloid article in JPCB.



You should read the article to understand why I did what I did in the tutorial, 
and then move on to reading articles that are more similar to your case.  These 
will be much more relevant to what you're doing.


-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] ligand moving out during umbrella sampling

[abhisek Mondal]

On Sun, May 7, 2017 at 11:37 PM, Justin Lemkul  wrote:

>
>
> On 5/7/17 1:57 AM, abhisek Mondal wrote:
>
>> Hi,
>>
>> For your ease of understanding regarding what is happening during this
>> above said umbrella-mdrun, I have shared the trajectory video file the
>> following link.
>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>>
>> Is this normal given that the mdp code being used ? I basically have no
>> idea with this step, so please help me out. I'm using gromacs-4.6.2.
>>
>>
> Your setup is incorrect.  You're applying a biasing potential only along
> z, so the ligand can move freely along x and y.  A protein-ligand complex
> has spherical symmetry, so you should set the reaction coordinate to the
> vector connecting the ligand with some suitable subset of interacting
> protein residues.


I don't get it.
We are trying not to move our configuration (generated after pulling
simulation) along the reaction coordinate, so for restraining we are
supposed to set pull_rate1=0.0.
If applying biasing potential only along z is causing movement along x and
y then what if we apply the biasing potential along x,y,z ? Will it cause
any good in restraining the ligand?

Moreover, you said previously "A protein-ligand complex has spherical
symmetry, so you should set the reaction coordinate to the vector
connecting the ligand with some suitable subset of interacting protein
residues.". It is really unclear to me, could you please give me some
examples to understand it more simply? I had pulled the ligand along -z
axis, doesn't it mean that the reaction coordinate is to be that way ? The
fact that I'm struggling with is to restrain the pull configurations for
further sampling.

I'm really a beginner, so maybe I'm asking stupid questions. Please give me
some advise. I'm really unable to decipher the scenario in comparison to
your amyloid article in JPCB.


  You're following the tutorial too literally and that's not correct.  Also
> do not restrain the protein (I say this weekly; not enough people are
> reading the details of the tutorial and associated paper and just copying
> .mdp settings...)
>
> -Justin
>
>
>> On Sun, May 7, 2017 at 9:57 AM, abhisek Mondal 
>> wrote:
>>
>> Hi,
>>>
>>> I have completed pulling as per the tutorial stated. But having a strange
>>> issue during umbrella sampling. When I execute:
>>> *mpirun -np 320 /app/gromacs462/bin/mdrun_mpi -v -deffnm umbrella8 -pf
>>> pullf-umbrella8.xvg -px pullx-umbrella8.xvg*
>>>
>>> The gro file generated at the end shows the ligand is way far compared to
>>> starting position, as if another pulling is done !
>>> Please suggest me a way to tackle this issue. If this thing happens to
>>> all
>>> the configurations generated during pulling then how am I supposed to get
>>> the PMF ?
>>>
>>> The md_umbrella.mdp I'm using is:
>>> title   = Umbrella pulling simulation
>>> define  = -DPOSRES
>>> ; Run parameters
>>> integrator  = md
>>> dt  = 0.002
>>> tinit   = 0
>>> nsteps  = 500   ; 10 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_ngroups= 1
>>> pull_group0 = Protein_chain_A
>>> pull_group1 = ACO
>>> pull_geometry   = direction
>>> pull_dim= N N Y ; pulling in Z dimension
>>> pull_rate1  = 0.0
>>> pull_k1 = 1000   ; kJ mol^-1 nm^-2
>>> pull_start  = yes   ; define initial COM distance > 0
>>> pull_vec1   = 0 0 -1
>>>
>>> My question is despite the pull_rate1 being 0.0, why the ligand is moving
>>> ? Is it the pull_start or something else I'm missing here resulting in
>>> such
>>> 

Re: [gmx-users] ligand moving out during umbrella sampling

[Justin Lemkul]

On 5/7/17 2:22 PM, abhisek Mondal wrote:

Hello Justin,
Thank you for the explanation. I'm really new to the field so choosing
factors in a bit confusion.

You said in this set up the ligand can still move around X and Y direction.
My question is what if I set pull_k1=0? The ligand also won't move this
way.


If you set pull_k1 to zero, it won't accomplish anything at all.  You'll have no 
biasing force.



You mentioned that during this run we want to restrain the ligand or don't
want to change the configuration generated by pulling simulation.
Is this approach right?



I don't understand the second question.

-Justin




On May 7, 2017 11:37 PM, "Justin Lemkul"  wrote:



On 5/7/17 1:57 AM, abhisek Mondal wrote:


Hi,

For your ease of understanding regarding what is happening during this
above said umbrella-mdrun, I have shared the trajectory video file the
following link.
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

Is this normal given that the mdp code being used ? I basically have no
idea with this step, so please help me out. I'm using gromacs-4.6.2.



Your setup is incorrect.  You're applying a biasing potential only along z,
so the ligand can move freely along x and y.  A protein-ligand complex has
spherical symmetry, so you should set the reaction coordinate to the vector
connecting the ligand with some suitable subset of interacting protein
residues.  You're following the tutorial too literally and that's not
correct.  Also do not restrain the protein (I say this weekly; not enough
people are reading the details of the tutorial and associated paper and
just copying .mdp settings...)

-Justin



On Sun, May 7, 2017 at 9:57 AM, abhisek Mondal 
wrote:

Hi,


I have completed pulling as per the tutorial stated. But having a strange
issue during umbrella sampling. When I execute:
*mpirun -np 320 /app/gromacs462/bin/mdrun_mpi -v -deffnm umbrella8 -pf
pullf-umbrella8.xvg -px pullx-umbrella8.xvg*

The gro file generated at the end shows the ligand is way far compared to
starting position, as if another pulling is done !
Please suggest me a way to tackle this issue. If this thing happens to all
the configurations generated during pulling then how am I supposed to get
the PMF ?

The md_umbrella.mdp I'm using is:
title   = Umbrella pulling simulation
define  = -DPOSRES
; Run parameters
integrator  = md
dt  = 0.002
tinit   = 0
nsteps  = 500   ; 10 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_ngroups= 1
pull_group0 = Protein_chain_A
pull_group1 = ACO
pull_geometry   = direction
pull_dim= N N Y ; pulling in Z dimension
pull_rate1  = 0.0
pull_k1 = 1000   ; kJ mol^-1 nm^-2
pull_start  = yes   ; define initial COM distance > 0
pull_vec1   = 0 0 -1

My question is despite the pull_rate1 being 0.0, why the ligand is moving
? Is it the pull_start or something else I'm missing here resulting in
such
a crash ?

Your suggestions will be highly appreciated.
Thank you.

--
Abhisek Mondal

*Senior Research Fellow*

*Structural Biology and Bioinformatics Division*
*CSIR-Indian Institute of Chemical Biology*

*Kolkata 700032*

*INDIA*








--
==

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? 

Re: [gmx-users] ligand moving out during umbrella sampling

[abhisek Mondal]

Hello Justin,
Thank you for the explanation. I'm really new to the field so choosing
factors in a bit confusion.

You said in this set up the ligand can still move around X and Y direction.
My question is what if I set pull_k1=0? The ligand also won't move this
way.
You mentioned that during this run we want to restrain the ligand or don't
want to change the configuration generated by pulling simulation.
Is this approach right?



On May 7, 2017 11:37 PM, "Justin Lemkul"  wrote:



On 5/7/17 1:57 AM, abhisek Mondal wrote:

> Hi,
>
> For your ease of understanding regarding what is happening during this
> above said umbrella-mdrun, I have shared the trajectory video file the
> following link.
> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>
> Is this normal given that the mdp code being used ? I basically have no
> idea with this step, so please help me out. I'm using gromacs-4.6.2.
>
>
Your setup is incorrect.  You're applying a biasing potential only along z,
so the ligand can move freely along x and y.  A protein-ligand complex has
spherical symmetry, so you should set the reaction coordinate to the vector
connecting the ligand with some suitable subset of interacting protein
residues.  You're following the tutorial too literally and that's not
correct.  Also do not restrain the protein (I say this weekly; not enough
people are reading the details of the tutorial and associated paper and
just copying .mdp settings...)

-Justin


> On Sun, May 7, 2017 at 9:57 AM, abhisek Mondal 
> wrote:
>
> Hi,
>>
>> I have completed pulling as per the tutorial stated. But having a strange
>> issue during umbrella sampling. When I execute:
>> *mpirun -np 320 /app/gromacs462/bin/mdrun_mpi -v -deffnm umbrella8 -pf
>> pullf-umbrella8.xvg -px pullx-umbrella8.xvg*
>>
>> The gro file generated at the end shows the ligand is way far compared to
>> starting position, as if another pulling is done !
>> Please suggest me a way to tackle this issue. If this thing happens to all
>> the configurations generated during pulling then how am I supposed to get
>> the PMF ?
>>
>> The md_umbrella.mdp I'm using is:
>> title   = Umbrella pulling simulation
>> define  = -DPOSRES
>> ; Run parameters
>> integrator  = md
>> dt  = 0.002
>> tinit   = 0
>> nsteps  = 500   ; 10 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_ngroups= 1
>> pull_group0 = Protein_chain_A
>> pull_group1 = ACO
>> pull_geometry   = direction
>> pull_dim= N N Y ; pulling in Z dimension
>> pull_rate1  = 0.0
>> pull_k1 = 1000   ; kJ mol^-1 nm^-2
>> pull_start  = yes   ; define initial COM distance > 0
>> pull_vec1   = 0 0 -1
>>
>> My question is despite the pull_rate1 being 0.0, why the ligand is moving
>> ? Is it the pull_start or something else I'm missing here resulting in
>> such
>> a crash ?
>>
>> Your suggestions will be highly appreciated.
>> Thank you.
>>
>> --
>> Abhisek Mondal
>>
>> *Senior Research Fellow*
>>
>> *Structural Biology and Bioinformatics Division*
>> *CSIR-Indian Institute of Chemical Biology*
>>
>> *Kolkata 700032*
>>
>> *INDIA*
>>
>>
>
>
>
-- 
==

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 

Re: [gmx-users] ligand moving out during umbrella sampling

[Justin Lemkul]

On 5/7/17 1:57 AM, abhisek Mondal wrote:

Hi,

For your ease of understanding regarding what is happening during this
above said umbrella-mdrun, I have shared the trajectory video file the
following link.
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

Is this normal given that the mdp code being used ? I basically have no
idea with this step, so please help me out. I'm using gromacs-4.6.2.



Your setup is incorrect.  You're applying a biasing potential only along z, so 
the ligand can move freely along x and y.  A protein-ligand complex has 
spherical symmetry, so you should set the reaction coordinate to the vector 
connecting the ligand with some suitable subset of interacting protein residues. 
 You're following the tutorial too literally and that's not correct.  Also do 
not restrain the protein (I say this weekly; not enough people are reading the 
details of the tutorial and associated paper and just copying .mdp settings...)


-Justin



On Sun, May 7, 2017 at 9:57 AM, abhisek Mondal 
wrote:


Hi,

I have completed pulling as per the tutorial stated. But having a strange
issue during umbrella sampling. When I execute:
*mpirun -np 320 /app/gromacs462/bin/mdrun_mpi -v -deffnm umbrella8 -pf
pullf-umbrella8.xvg -px pullx-umbrella8.xvg*
The gro file generated at the end shows the ligand is way far compared to
starting position, as if another pulling is done !
Please suggest me a way to tackle this issue. If this thing happens to all
the configurations generated during pulling then how am I supposed to get
the PMF ?

The md_umbrella.mdp I'm using is:
title   = Umbrella pulling simulation
define  = -DPOSRES
; Run parameters
integrator  = md
dt  = 0.002
tinit   = 0
nsteps  = 500   ; 10 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_ngroups= 1
pull_group0 = Protein_chain_A
pull_group1 = ACO
pull_geometry   = direction
pull_dim= N N Y ; pulling in Z dimension
pull_rate1  = 0.0
pull_k1 = 1000   ; kJ mol^-1 nm^-2
pull_start  = yes   ; define initial COM distance > 0
pull_vec1   = 0 0 -1

My question is despite the pull_rate1 being 0.0, why the ligand is moving
? Is it the pull_start or something else I'm missing here resulting in such
a crash ?

Your suggestions will be highly appreciated.
Thank you.

--
Abhisek Mondal

*Senior Research Fellow*

*Structural Biology and Bioinformatics Division*
*CSIR-Indian Institute of Chemical Biology*

*Kolkata 700032*

*INDIA*







--
==

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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mail to gmx-users-requ...@gromacs.org.

Re: [gmx-users] ligand moving out during umbrella sampling

[abhisek Mondal]

Hi,

For your ease of understanding regarding what is happening during this
above said umbrella-mdrun, I have shared the trajectory video file the
following link.
https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0

Is this normal given that the mdp code being used ? I basically have no
idea with this step, so please help me out. I'm using gromacs-4.6.2.


On Sun, May 7, 2017 at 9:57 AM, abhisek Mondal 
wrote:

> Hi,
>
> I have completed pulling as per the tutorial stated. But having a strange
> issue during umbrella sampling. When I execute:
> *mpirun -np 320 /app/gromacs462/bin/mdrun_mpi -v -deffnm umbrella8 -pf
> pullf-umbrella8.xvg -px pullx-umbrella8.xvg*
> The gro file generated at the end shows the ligand is way far compared to
> starting position, as if another pulling is done !
> Please suggest me a way to tackle this issue. If this thing happens to all
> the configurations generated during pulling then how am I supposed to get
> the PMF ?
>
> The md_umbrella.mdp I'm using is:
> title   = Umbrella pulling simulation
> define  = -DPOSRES
> ; Run parameters
> integrator  = md
> dt  = 0.002
> tinit   = 0
> nsteps  = 500   ; 10 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_ngroups= 1
> pull_group0 = Protein_chain_A
> pull_group1 = ACO
> pull_geometry   = direction
> pull_dim= N N Y ; pulling in Z dimension
> pull_rate1  = 0.0
> pull_k1 = 1000   ; kJ mol^-1 nm^-2
> pull_start  = yes   ; define initial COM distance > 0
> pull_vec1   = 0 0 -1
>
> My question is despite the pull_rate1 being 0.0, why the ligand is moving
> ? Is it the pull_start or something else I'm missing here resulting in such
> a crash ?
>
> Your suggestions will be highly appreciated.
> Thank you.
>
> --
> Abhisek Mondal
>
> *Senior Research Fellow*
>
> *Structural Biology and Bioinformatics Division*
> *CSIR-Indian Institute of Chemical Biology*
>
> *Kolkata 700032*
>
> *INDIA*
>



-- 
Abhisek Mondal

*Senior Research Fellow*

*Structural Biology and Bioinformatics Division*
*CSIR-Indian Institute of Chemical Biology*

*Kolkata 700032*

*INDIA*
-- 
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.

[gmx-users] ligand moving out during umbrella sampling

[abhisek Mondal]

Hi,

I have completed pulling as per the tutorial stated. But having a strange
issue during umbrella sampling. When I execute:
*mpirun -np 320 /app/gromacs462/bin/mdrun_mpi -v -deffnm umbrella8 -pf
pullf-umbrella8.xvg -px pullx-umbrella8.xvg*
The gro file generated at the end shows the ligand is way far compared to
starting position, as if another pulling is done !
Please suggest me a way to tackle this issue. If this thing happens to all
the configurations generated during pulling then how am I supposed to get
the PMF ?

The md_umbrella.mdp I'm using is:
title   = Umbrella pulling simulation
define  = -DPOSRES
; Run parameters
integrator  = md
dt  = 0.002
tinit   = 0
nsteps  = 500   ; 10 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_ngroups= 1
pull_group0 = Protein_chain_A
pull_group1 = ACO
pull_geometry   = direction
pull_dim= N N Y ; pulling in Z dimension
pull_rate1  = 0.0
pull_k1 = 1000   ; kJ mol^-1 nm^-2
pull_start  = yes   ; define initial COM distance > 0
pull_vec1   = 0 0 -1

My question is despite the pull_rate1 being 0.0, why the ligand is moving ?
Is it the pull_start or something else I'm missing here resulting in such a
crash ?

Your suggestions will be highly appreciated.
Thank you.

-- 
Abhisek Mondal

*Senior Research Fellow*

*Structural Biology and Bioinformatics Division*
*CSIR-Indian Institute of Chemical Biology*

*Kolkata 700032*

*INDIA*
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