Chris, I think you are correct here. For binding calculations there is probably a further trick relating to how to define an unbound state that has a well-defined concentration. This I think depends on how one is pulling -- i.e. doing simple radial PMFs is probably a bad idea, because to even converge the PMF when the ligand is separate from the protein, you by definition need to integrate over all x, y, and z at that r, so you end up needing to sample a spherical shell covering a substantial fraction of the simulation box. For this reason I think it's probably wiser to do pulling along a specified vector away from the protein, for example (this is what people using this strategy have mostly done, I think). Additionally there is the standard state issue, which is important also.
I think you may have more or less raised all of these issues already; I'm just trying to put them a slightly different way. David On Wed, Apr 23, 2008 at 5:34 PM, <[EMAIL PROTECTED]> wrote: > That sentence could definitely use some massaging. Try this: > > Whether one needs to correct for this contribution depends on what the > pmf should represent. When one wants to pull a substrate into a protein, > this entropic term indeed contributes to the work to get the substrate > into the protein. This is because the work required to pull a ligand into a > protein binding pocket depends on the concentration of that ligand in the > unbound state. The entropic contribution, however, depends on the size of > your simulation box if your sampling of the entire box is ergodic. Further, > the large computational cost of converging the sampling of large separations > between the protein and ligand make it undesirable to target true ergodicity > for large separations. It is more efficient to calculate the work required > to pull a ligand into a protein from an unbound state that has a defined > concentration and then to separately calculate the work required to change > that concentration to some standard state, e.g. 1 molar. > > If any other free energy users care to comment, perhaps we could come up > with something based on what I have suggested (or something entirely > different) that could go into the new manual. > > --original message -- > > I sent the attached message on last March 31 but I didn't get any > answer... may be the right people was not available at that time and > that is why I am trying again. I would thank a lot to have some more > detail about this paragraph in the gromacs manual (version 3.3, chapter > 6, page 111): > > Whether one needs to correct for this contribution depends on what the > pmf should represent. When one wants to pull a substrate into a protein, > this entropic term indeed contributes to the work to get the substrate > into the protein. But when calculating a pmf between two solutes in a > solvent, for the purpose of simulating without solvent, the entropic > contribution should be removed. Note that this term can be significant; > when at 300K the distance is halved the contribution is 3.5 kJ mol-1." > > why exactly for a substrate-protein complex shouldn't one correct the > pmf? > > > > > _______________________________________________ > gmx-users mailing list gmx-users@gromacs.org > http://www.gromacs.org/mailman/listinfo/gmx-users > Please search the archive at http://www.gromacs.org/search before posting! > Please don't post (un)subscribe requests to the list. Use thewww interface > or send it to [EMAIL PROTECTED] > Can't post? Read http://www.gromacs.org/mailing_lists/users.php > _______________________________________________ gmx-users mailing list gmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to [EMAIL PROTECTED] Can't post? Read http://www.gromacs.org/mailing_lists/users.php