[gmx-users] Number of windows in umbrella sampling

Justin A. Lemkul jalemkul at vt.edu
Mon Feb 13 15:42:51 CET 2012

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 

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.


> Shahid Nayeem
> On Mon, Feb 13, 2012 at 7:15 PM, Justin A. Lemkul <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> | (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
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080


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