subject:"\[gmx\-users\] Number of windows in umbrella sampling"

Re: [gmx-users] Number of windows in umbrella sampling

2012-02-14 Thread Justin A. Lemkul




Justin A. Lemkul wrote:



shahid nayeem wrote:
Thanks Justin. I will try again. But please refer to some protocol if 
you know and one last question that before doing umbrella sampling 
simulation how can one be sure that the pulling is good and one should 
go ahead with selecting window and doing umbrella sampling. In the end 
when you see histo.xvg and profile.xvg , it cost a lot computationally 
and if you  don't get it right these computational resources are wasted. 


There are certainly simulations that have been published using umbrella 
sampling on a variety of systems.  I'm sure some relatively quick 
literature searching will lead you to some suitable ideas.  Spending a 
few hours doing some reading will save you months of wasted CPU time.




I should, of course, mention that what you have done is not necessarily wasted, 
it's simply insufficient.  Simulations can always be extended and new umbrella 
sampling windows added after the fact and incorporated into the analysis.  A 
better experimental plan will save these headaches in the future.


-Justin

--


Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin


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Re: [gmx-users] Number of windows in umbrella sampling

2012-02-14 Thread Justin A. Lemkul

shahid nayeem wrote:
Thanks Justin. I will try again. But please refer to some protocol if 
you know and one last question that before doing umbrella sampling 
simulation how can one be sure that the pulling is good and one should 
go ahead with selecting window and doing umbrella sampling. In the end 
when you see histo.xvg and profile.xvg , it cost a lot computationally 
and if you  don't get it right these computational resources are wasted. 

There are certainly simulations that have been published using umbrella sampling 
on a variety of systems.  I'm sure some relatively quick literature searching 
will lead you to some suitable ideas.  Spending a few hours doing some reading 
will save you months of wasted CPU time.

-Justin

Shahid nayeem

On Mon, Feb 13, 2012 at 8:12 PM, Justin A. Lemkul > wrote:

shahid nayeem wrote:

Thanks for quick reply. I have created mutant of a complex by
changing interface residue in VMD. These mutant are
experimentally known to show less binding affinity. I want to
reproduce these results with umbrella sampling. Now I am sending
profile and histo file for wt and mutant. Please suggest where i
am wrong.

The PMF curves look poorly converged.  Your reaction coordinates are
not the same for both the WT and mutant (you appear to have a far
shorter reaction coordinate for the mutant).  The energy minimum is
also ill-defined for the mutant.

As for the reason behind these phenomena, I cannot say, nor do I
have time to sort through your data and try to work it out for you.
 Refer to the literature, find similar protocols, and proceed from
there.

-Justin

Shahid Nayeem

On Mon, Feb 13, 2012 at 7:15 PM, Justin A. Lemkul
mailto:jalem...@vt.edu>
>> wrote:

   shahid nayeem wrote:

   Dear Justin
   I am doing umbrella pulling simulation of a protein
complex wt
   and mutant. I expect mutant to give lower deltG value. I am
   attaching a tif file of energy vs time curve of wt and mutant
   protein on pulling simulation. These energies are obtained by
   g_energy and selecting 11 option which is COM pulling
energy. In
   this curve the first peak decreases and again rises at longer
   time. How many windows should be selected. As expected
the peak
   of COM pulling energy is lower in mutants. Please explain why
   the energy again rises at higher time. Should I use the
windows
   upto 160ps only because thereafter in both curve there is
rise
   in energy value. the pull code used is as follows.

   What you have obtained is a path-dependent energy that may or may
   not signify anything useful - it almost certainly does not.  I
   cannot offer an explanation of the sharp increase towards the
end of
   the simulation other than to speculate that your box is of
   insufficient size and you're encountering PBC issues.

   As for how many windows are necessary, it's also impossible
to tell.
You need enough windows to adequately sample the reaction
   coordinate.  Thus, it is decided based on how far you need to
   separate the two species, how strong the force constant is during
   the US simulations, the nature of the interactions in the
system and
   how fast they converge, etc.

   -Justin

   pull_geometry   = distance pull_dim= Y N  Y
   pull_vec1   = 0.75 0  1
   pull_start  = yes  pull_ngroups= 1
   pull_group0 = Chain_B pull_group1 = Chain_A
pull_rate1 = 0.01  pull_k1 = 1000

   -- ====

   Justin A. Lemkul
   Ph.D. Candidate
   ICTAS Doctoral Scholar
   MILES-IGERT Trainee
   Department of Biochemistry
   Virginia Tech
   Blacksburg, VA
   jalemkul[at]vt.edu   | (540)
231-9080
   http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

   >

   ====

   -- gmx-users mailing listgmx-users@gromacs.org

   >
   http://lists.gromacs.org/mailman/listinfo/gmx-users

Re: [gmx-users] Number of windows in umbrella sampling

2012-02-13 Thread shahid nayeem

Thanks Justin. I will try again. But please refer to some protocol if you
know and one last question that before doing umbrella sampling simulation
how can one be sure that the pulling is good and one should go ahead with
selecting window and doing umbrella sampling. In the end when you see
histo.xvg and profile.xvg , it cost a lot computationally and if you
 don't get it right these computational resources are wasted.
Shahid nayeem

On Mon, Feb 13, 2012 at 8:12 PM, Justin A. Lemkul  wrote:

>
>
> shahid nayeem wrote:
>
>> Thanks for quick reply. I have created mutant of a complex by changing
>> interface residue in VMD. These mutant are experimentally known to show
>> less binding affinity. I want to reproduce these results with umbrella
>> sampling. Now I am sending profile and histo file for wt and mutant. Please
>> suggest where i am wrong.
>>
>
> The PMF curves look poorly converged.  Your reaction coordinates are not
> the same for both the WT and mutant (you appear to have a far shorter
> reaction coordinate for the mutant).  The energy minimum is also
> ill-defined for the mutant.
>
> As for the reason behind these phenomena, I cannot say, nor do I have time
> to sort through your data and try to work it out for you.  Refer to the
> literature, find similar protocols, and proceed from there.
>
> -Justin
>
>  Shahid Nayeem
>>
>>
>> On Mon, Feb 13, 2012 at 7:15 PM, Justin A. Lemkul > jalem...@vt.edu>> wrote:
>>
>>
>>
>>shahid nayeem wrote:
>>
>>Dear Justin
>>I am doing umbrella pulling simulation of a protein complex wt
>>and mutant. I expect mutant to give lower deltG value. I am
>>attaching a tif file of energy vs time curve of wt and mutant
>>protein on pulling simulation. These energies are obtained by
>>g_energy and selecting 11 option which is COM pulling energy. In
>>this curve the first peak decreases and again rises at longer
>>time. How many windows should be selected. As expected the peak
>>of COM pulling energy is lower in mutants. Please explain why
>>the energy again rises at higher time. Should I use the windows
>>upto 160ps only because thereafter in both curve there is rise
>>in energy value. the pull code used is as follows.
>>
>>
>>What you have obtained is a path-dependent energy that may or may
>>not signify anything useful - it almost certainly does not.  I
>>cannot offer an explanation of the sharp increase towards the end of
>>the simulation other than to speculate that your box is of
>>insufficient size and you're encountering PBC issues.
>>
>>As for how many windows are necessary, it's also impossible to tell.
>> You need enough windows to adequately sample the reaction
>>coordinate.  Thus, it is decided based on how far you need to
>>separate the two species, how strong the force constant is during
>>the US simulations, the nature of the interactions in the system and
>>how fast they converge, etc.
>>
>>-Justin
>>
>>
>>pull_geometry   = distance pull_dim= Y N  Y
>>pull_vec1   = 0.75 0  1
>>pull_start  = yes  pull_ngroups= 1
>>pull_group0 = Chain_B pull_group1 = Chain_A pull_rate1
>> = 0.01  pull_k1 = 1000
>>
>>-- ==**__==
>>
>>
>>Justin A. Lemkul
>>Ph.D. Candidate
>>ICTAS Doctoral Scholar
>>MILES-IGERT Trainee
>>Department of Biochemistry
>>Virginia Tech
>>Blacksburg, VA
>>jalemkul[at]vt.edu  | (540) 231-9080
>>
>> http://www.bevanlab.biochem.__**vt.edu/Pages/Personal/justin
>>
>> 
>> >
>>
>>==**__==
>>
>>-- gmx-users mailing listgmx-users@gromacs.org
>>
>>
>> http://lists.gromacs.org/__**mailman/listinfo/gmx-users
>>
>>
>> 
>> >
>>Please search the archive at
>>
>> http://www.gromacs.org/__**Support/Mailing_Lists/Search
>>
>>
>> >
>> before posting!
>>Please don't post (un)subscribe requests to the list. Use the www
>>interface or send it to gmx-users-requ...@gromacs.org
>>> >.
>>Can't post? Read 
>> http://www.gromacs.org/__**Support/Mailing_Lists
>>
>> 
>> >
>>
>>
>>
> --

Re: [gmx-users] Number of windows in umbrella sampling

2012-02-13 Thread Justin A. Lemkul




shahid nayeem wrote:
Thanks for quick reply. I have created mutant of a complex by changing 
interface residue in VMD. These mutant are experimentally known to show 
less binding affinity. I want to reproduce these results with umbrella 
sampling. Now I am sending profile and histo file for wt and mutant. 
Please suggest where i am wrong.


The PMF curves look poorly converged.  Your reaction coordinates are not the 
same for both the WT and mutant (you appear to have a far shorter reaction 
coordinate for the mutant).  The energy minimum is also ill-defined for the 
mutant.


As for the reason behind these phenomena, I cannot say, nor do I have time to 
sort through your data and try to work it out for you.  Refer to the literature, 
find similar protocols, and proceed from there.


-Justin


Shahid Nayeem

On Mon, Feb 13, 2012 at 7:15 PM, Justin A. Lemkul > wrote:




shahid nayeem wrote:

Dear Justin
I am doing umbrella pulling simulation of a protein complex wt
and mutant. I expect mutant to give lower deltG value. I am
attaching a tif file of energy vs time curve of wt and mutant
protein on pulling simulation. These energies are obtained by
g_energy and selecting 11 option which is COM pulling energy. In
this curve the first peak decreases and again rises at longer
time. How many windows should be selected. As expected the peak
of COM pulling energy is lower in mutants. Please explain why
the energy again rises at higher time. Should I use the windows
upto 160ps only because thereafter in both curve there is rise
in energy value. the pull code used is as follows.


What you have obtained is a path-dependent energy that may or may
not signify anything useful - it almost certainly does not.  I
cannot offer an explanation of the sharp increase towards the end of
the simulation other than to speculate that your box is of
insufficient size and you're encountering PBC issues.

As for how many windows are necessary, it's also impossible to tell.
 You need enough windows to adequately sample the reaction
coordinate.  Thus, it is decided based on how far you need to
separate the two species, how strong the force constant is during
the US simulations, the nature of the interactions in the system and
how fast they converge, etc.

-Justin


pull_geometry   = distance pull_dim= Y N  Y
pull_vec1   = 0.75 0  1
pull_start  = yes  pull_ngroups= 1
pull_group0 = Chain_B pull_group1 = Chain_A pull_rate1  
   = 0.01  pull_k1 = 1000



-- 
==__==


Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu  | (540) 231-9080
http://www.bevanlab.biochem.__vt.edu/Pages/Personal/justin


==__==
-- 
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 before posting!
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--


Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin


--
gmx-users mailing listgmx-users@gromacs.org
http://lists.gromacs.org/mailman/listinfo/gmx-users
Please search the archive at 
http://www.gromacs.org/Support/Mailing_Lists/Search before posting!
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Re: [gmx-users] Number of windows in umbrella sampling

2012-02-13 Thread Justin A. Lemkul




shahid nayeem wrote:

Dear Justin
I am doing umbrella pulling simulation of a protein complex wt and 
mutant. I expect mutant to give lower deltG value. I am attaching a tif 
file of energy vs time curve of wt and mutant protein on pulling 
simulation. These energies are obtained by g_energy and selecting 11 
option which is COM pulling energy. In this curve the first peak 
decreases and again rises at longer time. How many windows should be 
selected. As expected the peak of COM pulling energy is lower in 
mutants. Please explain why the energy again rises at higher time. 
Should I use the windows upto 160ps only because thereafter in both 
curve there is rise in energy value. the pull code used is as follows.




What you have obtained is a path-dependent energy that may or may not signify 
anything useful - it almost certainly does not.  I cannot offer an explanation 
of the sharp increase towards the end of the simulation other than to speculate 
that your box is of insufficient size and you're encountering PBC issues.


As for how many windows are necessary, it's also impossible to tell.  You need 
enough windows to adequately sample the reaction coordinate.  Thus, it is 
decided based on how far you need to separate the two species, how strong the 
force constant is during the US simulations, the nature of the interactions in 
the system and how fast they converge, etc.


-Justin

pull_geometry   = distance 
pull_dim= Y N  Y

pull_vec1   = 0.75 0  1
pull_start  = yes  
pull_ngroups= 1
pull_group0 = Chain_B 
pull_group1 = Chain_A 
pull_rate1  = 0.01  
pull_k1 = 1000 



--


Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin


--
gmx-users mailing listgmx-users@gromacs.org
http://lists.gromacs.org/mailman/listinfo/gmx-users
Please search the archive at 
http://www.gromacs.org/Support/Mailing_Lists/Search before posting!
Please don't post (un)subscribe requests to the list. Use the 
www interface or send it to gmx-users-requ...@gromacs.org.

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Re: [gmx-users] Number of windows in umbrella sampling

Re: [gmx-users] Number of windows in umbrella sampling

Re: [gmx-users] Number of windows in umbrella sampling

Re: [gmx-users] Number of windows in umbrella sampling

Re: [gmx-users] Number of windows in umbrella sampling

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