[gmx-users] pulling force vs free energy

[Sai Kumar Ramadugu]

I agree with Justin. I have tried myself several SMD simulations for ligand
binding studies. I tried 500 simulations and not sure if they are enough.
Further, the path dependence is very important part.
For different paths that you can try, look at McCammon group's paper in
JACS 128, 3019-3026. There are several other papers too, but this discusses
about various methods that you can try to get the pmf using Jarzynski

On Wed, Nov 16, 2011 at 9:25 AM, Justin A. Lemkul <jalemkul at vt.edu> wrote:

>
>
> Vijayaraj wrote:
>
>>
>>
>>    Message: 4
>>    Date: Wed, 16 Nov 2011 09:34:02 -0500
>>    From: "Justin A. Lemkul" <jalemkul at vt.edu <mailto:jalemkul at vt.edu>>
>>
>>    Subject: Re: [gmx-users] pulling force vs free energy
>>    To: Discussion list for GROMACS users <gmx-users at gromacs.org
>>    <mailto:gmx-users at gromacs.org>**>
>>    Message-ID: <4EC3C9DA.7040400 at vt.edu <mailto:4EC3C9DA.7040400 at vt.**edu<4EC3C9DA.7040400 at vt.edu>
>> >>
>>
>>    Content-Type: text/plain; charset=ISO-8859-1; format=flowed
>>
>>
>>
>>    Vijayaraj wrote:
>>     > Hi,
>>     >
>>     > What is the relation between pulling force and free energy of
>>    binding.
>>     > can we relate the maximum pulling force with the free energy. for
>>     > example, 2 systems has the maximum pulling force and free energy as
>>     > below from umbrella sampling and g_wham analysis,
>>     >
>>     >                       max. force        free energy
>>     > system 1          1470                42
>>     > system 2          1647                32
>>     >
>>     > system 2 has higher pulling force than system 1 and the free energy
>>     > result is different from this trend.
>>     >
>>
>>    How did you obtain the maximum force, just a single SMD trajectory?
>>     If so, I
>>    wouldn't put a lot of faith in it necessarily.  Umbrella sampling is
>>    a more
>>    robust method than a single pull.  You can use large numbers of pulling
>>    simulations and apply Jarzynski's equation to calculate free energy,
>>    but there
>>    are distinct caveats (although I suppose there are caveats with any
>>    method).
>>
>>    -Justin
>>
>>
>> yes. the max force is obtained from single SMD trajectory. So in this
>> case we dont have to worry about the correction between max. force and free
>> energy. I found one of my free energy result is 2 times larger than the
>> previous result, where they have applied Jarzynski's equation.
>>
>>
> SMD is path-dependent, while a true DeltaG is a path-independent quantity.
> Hence why you cannot easily connect the two.  Convergence in sampling and
> limitations in each technique make it sometimes hard to compare the results
> that others have obtained with other methods.  Proper data collection for
> Jarzynski's method requires exhaustive sampling, which is often hard to
> obtain (not a blind criticism of others' work, just a fact).
>
> -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<http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin>
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