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<div>In general a realistic unfolded system would have to start at several random points in state A, and allowing it to fold into state B. This accounts for gaussian distributions of random states...</div>
<div><br/>
these tend to be long as the folding process is between 200 (for short) to 5-6 usecounds for longer proteins...</div>
<div> </div>
<div>Some tricks...</div>
<div> </div>
<div>1) starting from a half folded state, however this will not give your entire energy system from A to B</div>
<div>2) setting up the system with a chaperone protein (structures are in the PDB)...this gives a more rapid, but biological vs. in solvent state...</div>
<div>3) Reducing your system size, as unfolded proteins take up more volumn in a unit cell, thus every 20-40 nanoseconds, stop, reduce the unit cell volumn, then continue, which allows the larger scale simulations to be achieved much faster</div>
<div> </div>
<div>The bar method works great for smaller molecules, but not proteins, as it if you read the paper is based on constants derived from a few hundred real kinetic determined states for small molecules. These are not a linear curve for proteins, and are usually protein specific, or even larger molecule specific if you go higher than 100 atoms...</div>
<div> </div>
<div>Dont know what your doing though...</div>
<div> </div>
<div>Sincerely,</div>
<div> </div>
<div>Stephan L. Watkins, PhD</div>
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<div style="margin:0 0 10px 0;"><b>Gesendet:</b> Sonntag, 19. April 2015 um 03:41 Uhr<br/>
<b>Von:</b> "Christopher Neale" <chris.neale@alum.utoronto.ca><br/>
<b>An:</b> "gromacs.org_gmx-users@maillist.sys.kth.se" <gromacs.org_gmx-users@maillist.sys.kth.se>, "gmx-users@gromacs.org" <gmx-users@gromacs.org><br/>
<b>Betreff:</b> Re: [gmx-users] calculating free energy</div>
<div name="quoted-content">How about temperature replica exchange with de novo folding, then convert the probabilities of the folded and unfolded states into a free energy difference? You'll obviously need to be really careful about cutting off a sufficient amount of initial simulation time as equilibration, but you might be able to get a good idea of how much to cut if you repeated it once from unfolded and once from folded.<br/>
<br/>
Chris.<br/>
<br/>
________________________________________<br/>
From: gromacs.org_gmx-users-bounces@maillist.sys.kth.se <gromacs.org_gmx-users-bounces@maillist.sys.kth.se> on behalf of nazli kashani javid <nazlikjavid@gmail.com><br/>
Sent: 18 April 2015 11:24<br/>
To: gromacs.org_gmx-users@maillist.sys.kth.se<br/>
Subject: [gmx-users] calculating free energy<br/>
<br/>
Hi all,<br/>
<br/>
I know there are some methods for calculating free energy of* binding*<br/>
between a ligand and a receptor.<br/>
<br/>
1.Are there any methods for calculating free energy of *unfolding *proteins?<br/>
<br/>
4_helix bundle protein makes my system,<br/>
<br/>
2.Is scientifically reasonable for my system to calculate free energy in<br/>
the same way as described in tutorial number 6, methane in water ( coupling<br/>
parameter : vdw interaction)?<br/>
<br/>
Thank you<br/>
<br/>
any help is appreciated.<br/>
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