[gmx-users] Number of windows in umbrella sampling

Justin A. Lemkul jalemkul at vt.edu
Tue Feb 14 15:02:29 CET 2012



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 <jalemkul at vt.edu 
> <mailto:jalemkul at vt.edu>> 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
>         <jalemkul at vt.edu <mailto:jalemkul at vt.edu>
>         <mailto:jalemkul at vt.edu <mailto:jalemkul at 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 <http://vt.edu> <http://vt.edu> | (540)
>         231-9080
>            http://www.bevanlab.biochem.____vt.edu/Pages/Personal/justin
>         <http://vt.edu/Pages/Personal/justin>
>            <http://www.bevanlab.biochem.__vt.edu/Pages/Personal/justin
>         <http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin>>
> 
>            ==============================____==========
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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 <http://vt.edu> | (540) 231-9080
>     http://www.bevanlab.biochem.__vt.edu/Pages/Personal/justin
>     <http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin>
> 
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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

========================================



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