[gmx-users] Umbrella Sampling - Ligand Protein

[Justin A. Lemkul]

Steven Neumann wrote:
> 
> 
> On Mon, Mar 12, 2012 at 11:06 AM, Justin A. Lemkul <jalemkul at vt.edu 
> <mailto:jalemkul at vt.edu>> wrote:
> 
> 
> 
>     Steven Neumann wrote:
> 
> 
> 
>         On Sun, Mar 11, 2012 at 10:13 PM, Justin A. Lemkul
>         <jalemkul at vt.edu <mailto:jalemkul at vt.edu>
>         <mailto:jalemkul at vt.edu <mailto:jalemkul at vt.edu>>> wrote:
> 
> 
> 
>            Steven Neumann wrote:
> 
>                Hi Justin,
>                 As you advised I reduced number of my windows and I obtined
>                histogram:
>                 http://speedy.sh/2b9dT/histo.____JPG
>         <http://speedy.sh/2b9dT/histo.__JPG>
> 
>                <http://speedy.sh/2b9dT/histo.__JPG
>         <http://speedy.sh/2b9dT/histo.JPG>>
>                 Which looks really good.
>                The corresponding profile:
>                 http://speedy.sh/y8Ssz/____profile.JPG
>         <http://speedy.sh/y8Ssz/__profile.JPG>
> 
>                <http://speedy.sh/y8Ssz/__profile.JPG
>         <http://speedy.sh/y8Ssz/profile.JPG>>
>                 I do not understand it. Does my deltaG of binding
>         correspond to
>                everything above 0 kcal/mol which is 6 kcal/mol?
>                
> 
>            DeltaG = the free energy difference between the final and initial
>            states.  So that's up to you to decide.  Your curve is rather
>         rough
>            and the energy minimum potentially still ill-defined.  The
>            histograms indicate that the sampling overlap is likely fine, you
>            just may need a bit more sampling in each window to smooth things
>            out.  Also make use of the error estimates that g_wham can
>         provide;
>            they can be quite informative (and necessary).
> 
>            -Justin
> 
> 
>          Thank you Justin. In each window I run the simulation of 10 ns.
>         Do you think that making it 20 ns will make the profile more smooth?
>          
> 
> 
>     It's no use to blindly guess.  It's up to you to assess the
>     convergence of your simulations and decide on an appropriate time frame.
> 
>     -Justin
> 
>      
> 
> Thank you Justin. Is there any way to find out after deltaG the entropic 
> contribution to binding free energy?
>  

Probably, but having never done it I can't offer any specific guidance.  Perhaps 
others on the list can.  I would certainly suggest you seek a protocol in the 
literature; I feel sure that I've seen such endeavors.

-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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