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.<div>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<br>
<br><div class="gmail_quote">On Wed, Nov 16, 2011 at 9:25 AM, Justin A. Lemkul <span dir="ltr"><<a href="mailto:jalemkul@vt.edu">jalemkul@vt.edu</a>></span> wrote:<br><blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex;">
<br>
<br>
Vijayaraj wrote:<br>
<blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex"><div class="im">
<br>
<br>
Message: 4<br>
Date: Wed, 16 Nov 2011 09:34:02 -0500<br></div>
From: "Justin A. Lemkul" <<a href="mailto:jalemkul@vt.edu" target="_blank">jalemkul@vt.edu</a> <mailto:<a href="mailto:jalemkul@vt.edu" target="_blank">jalemkul@vt.edu</a>>><div class="im"><br>
Subject: Re: [gmx-users] pulling force vs free energy<br>
To: Discussion list for GROMACS users <<a href="mailto:gmx-users@gromacs.org" target="_blank">gmx-users@gromacs.org</a><br></div>
<mailto:<a href="mailto:gmx-users@gromacs.org" target="_blank">gmx-users@gromacs.org</a>><u></u>><br>
Message-ID: <<a href="mailto:4EC3C9DA.7040400@vt.edu" target="_blank">4EC3C9DA.7040400@vt.edu</a> <mailto:<a href="mailto:4EC3C9DA.7040400@vt.edu" target="_blank">4EC3C9DA.7040400@vt.<u></u>edu</a>>><div class="im">
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Content-Type: text/plain; charset=ISO-8859-1; format=flowed<br>
<br>
<br>
<br>
Vijayaraj wrote:<br>
> Hi,<br>
><br>
> What is the relation between pulling force and free energy of<br>
binding.<br>
> can we relate the maximum pulling force with the free energy. for<br>
> example, 2 systems has the maximum pulling force and free energy as<br>
> below from umbrella sampling and g_wham analysis,<br>
><br>
> max. force free energy<br>
> system 1 1470 42<br>
> system 2 1647 32<br>
><br>
> system 2 has higher pulling force than system 1 and the free energy<br>
> result is different from this trend.<br>
><br>
<br>
How did you obtain the maximum force, just a single SMD trajectory?<br>
If so, I<br>
wouldn't put a lot of faith in it necessarily. Umbrella sampling is<br>
a more<br>
robust method than a single pull. You can use large numbers of pulling<br>
simulations and apply Jarzynski's equation to calculate free energy,<br>
but there<br>
are distinct caveats (although I suppose there are caveats with any<br>
method).<br>
<br>
-Justin<br>
<br>
<br>
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.<br>
<br>
</div></blockquote>
<br>
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).<br>
<br>
-Justin<br>
<br>
-- <br>
==============================<u></u>==========<br>
<br>
Justin A. Lemkul<br>
Ph.D. Candidate<br>
ICTAS Doctoral Scholar<br>
MILES-IGERT Trainee<br>
Department of Biochemistry<br>
Virginia Tech<br>
Blacksburg, VA<br>
jalemkul[at]<a href="http://vt.edu" target="_blank">vt.edu</a> | <a href="tel:%28540%29%20231-9080" value="+15402319080" target="_blank">(540) 231-9080</a><br>
<a href="http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin" target="_blank">http://www.bevanlab.biochem.<u></u>vt.edu/Pages/Personal/justin</a><br>
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