[gmx-users] Entropy correction in PMF

[chris.neale at utoronto.ca]

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?