<html><head></head><body><div style="font-family: Verdana;font-size: 12.0px;"><div>
<div>You can also embed your protein-bound small molecule, protein unbound small molecule a good distance away in solvent of choice, then eq it at the proper temp/pressure. Then take several samples along an equed space, let them just run unrestrained, and you can calculate the energy change mean...same technique as the tutorial munus the pulled aspect. I posted something like this in response to a question Justin answered in a similar way, basically a single value with error estimates is generated, you have an A and B state with no in-between, with no energy curve, ie alot of work but single value. Since I posted this, I realized there are several older 1990's papers that did similar things, and there are large effects on the final affinity from simple solvent changes (salts/ions concentraition, other solvent molecules)...
<div name="quote" style="margin:10px 5px 5px 10px; padding: 10px 0 10px 10px; border-left:2px solid #C3D9E5; word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space;">
<div style="margin:0 0 10px 0;"><b>Gesendet:</b> Sonntag, 14. April 2013 um 13:24 Uhr<br/>
<b>Von:</b> "Justin Lemkul" <jalemkul@vt.edu><br/>
<b>An:</b> "Discussion list for GROMACS users" <gmx-users@gromacs.org><br/>
<b>Betreff:</b> Re: [gmx-users] Estimations of the drug's affinity</div>
<div name="quoted-content"><br/>
<br/>
On 4/14/13 2:13 AM, James Starlight wrote:<br/>
> Dear Gromacs users!<br/>
><br/>
> I wounder to know if it possible to simple estimate drug affinity by mean<br/>
> of MD simulation? As I know the drug's property is based on the free energy<br/>
> change of bound-unbound ligand. So It seems that Justin's tutorial (free<br/>
> energy calculations) might be usefull if it would not be so routine for the<br/>
> drugs ( in that workflow several coulombic-vdw interactions must be<br/>
> uncoupled). Is there any more easily way to perform such calculations for<br/>
> the typical small-drug compounds consisted of several non-covalent<br/>
> interactions with the receptors ?<br/>
><br/>
<br/>
Free energy calculations require considerable effort. You can approach the task<br/>
in a number of ways - FEP, BAR, TI, LIE, PMF, MM/PBSA, etc. There is a large<br/>
body of literature detailing methods for such calculations.<br/>
<br/>
-Justin<br/>
<br/>
--<br/>
========================================<br/>
<br/>
Justin A. Lemkul, Ph.D.<br/>
Research Scientist<br/>
Department of Biochemistry<br/>
Virginia Tech<br/>
Blacksburg, VA<br/>
jalemkul[at]vt.edu | (540) 231-9080<br/>
<a href="http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin" target="_blank">http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin</a><br/>
<br/>
========================================<br/>
--<br/>
gmx-users mailing list gmx-users@gromacs.org<br/>
<a href="http://lists.gromacs.org/mailman/listinfo/gmx-users" target="_blank">http://lists.gromacs.org/mailman/listinfo/gmx-users</a><br/>
* Please search the archive at <a href="http://www.gromacs.org/Support/Mailing_Lists/Search" target="_blank">http://www.gromacs.org/Support/Mailing_Lists/Search</a> before posting!<br/>
* Please don't post (un)subscribe requests to the list. Use the<br/>
www interface or send it to gmx-users-request@gromacs.org.<br/>
* Can't post? Read <a href="http://www.gromacs.org/Support/Mailing_Lists" target="_blank">http://www.gromacs.org/Support/Mailing_Lists</a></div>
</div>
</div>
</div></div></body></html>