[gmx-users] Entropy correction in PMF

[Berk Hess]

> Date: Wed, 23 Apr 2008 20:34:40 -0400
> From: chris.neale at utoronto.ca
> To: gmx-users at gromacs.org
> Subject: [gmx-users] Entropy correction in PMF
> 
> 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?

This is not a simple should or should not.
It depends on what you want to use the PMF for.

You should be aware that there is this simple entropic distance contribution.
When a substrate needs to enter into a protein, it has to work against
this entropic term. If you include this or not, depends on how your want
to present the PMF in a presentation, or how your will use it for further
calculation.

Berk.


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