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<body class='hmmessage'><div style="text-align: left;"><br></div><br><br><br><hr id="stopSpelling">> Date: Wed, 23 Apr 2008 20:34:40 -0400<br>> From: chris.neale@utoronto.ca<br>> To: gmx-users@gromacs.org<br>> Subject: [gmx-users] Entropy correction in PMF<br>> <br>> That sentence could definitely use some massaging. Try this:<br>> <br>> Whether one needs to correct for this contribution depends on what the<br>> pmf should represent. When one wants to pull a substrate into a protein,<br>> this entropic term indeed contributes to the work to get the substrate<br>> into the protein. This is because the work required to pull a ligand <br>> into a protein binding pocket depends on the concentration of that <br>> ligand in the unbound state. The entropic contribution, however, <br>> depends on the size of your simulation box if your sampling of the <br>> entire box is ergodic. Further, the large computational cost of <br>> converging the sampling of large separations between the protein and <br>> ligand make it undesirable to target true ergodicity for large <br>> separations. It is more efficient to calculate the work required to <br>> pull a ligand into a protein from an unbound state that has a defined <br>> concentration and then to separately calculate the work required to <br>> change that concentration to some standard state, e.g. 1 molar.<br>> <br>> If any other free energy users care to comment, perhaps we could come <br>> up with something based on what I have suggested (or something <br>> entirely different) that could go into the new manual.<br>> <br>> --original message --<br>> <br>> I sent the attached message on last March 31 but I didn't get any<br>> answer... may be the right people was not available at that time and<br>> that is why I am trying again. I would thank a lot to have some more<br>> detail about this paragraph in the gromacs manual (version 3.3, chapter<br>> 6, page 111):<br>> <br>> Whether one needs to correct for this contribution depends on what the<br>> pmf should represent. When one wants to pull a substrate into a protein,<br>> this entropic term indeed contributes to the work to get the substrate<br>> into the protein. But when calculating a pmf between two solutes in a<br>> solvent, for the purpose of simulating without solvent, the entropic<br>> contribution should be removed. Note that this term can be significant;<br>> when at 300K the distance is halved the contribution is 3.5 kJ mol-1.�<br>> <br>> why exactly for a substrate-protein complex shouldn't one correct the<br>> pmf?<br><br>This is not a simple should or should not.<br>It depends on what you want to use the PMF for.<br><br>You should be aware that there is this simple entropic distance contribution.<br>When a substrate needs to enter into a protein, it has to work against<br>this entropic term. If you include this or not, depends on how your want<br>to present the PMF in a presentation, or how your will use it for further<br>calculation.<br><br>Berk.<br><br><br /><hr />Express yourself instantly with MSN Messenger! <a href='http://clk.atdmt.com/AVE/go/onm00200471ave/direct/01/' target='_new'>MSN Messenger</a></body>
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