[gmx-users] Entropy correction in PMF

[Ángel Piñeiro]

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?


Angel Piñeiro.



On Sun, 2008-03-30 at 16:19 -0600, Ángel Piñeiro wrote:
> Dear all,
> 
>  
> 
> My question is related to the calculation of absolute binding Gibbs
> energies more than to the use of Gromacs but it is motivated by a
> paragraph of the Gromacs manual version 3.3 (and also on several
> papers by Gilson, Karplus, and others), so I hope someone can help me.
> 
>  
> 
> We have calculated the PMF curve along the distance between the center
> of mass of a cyclodextrin (an oligosaccharide with a hydrophobic
> cavity mimicking a pocket in a protein) and a surfactant of relatively
> short aliphatic chain. Following the work of Gilson (several papers
> published between 1997 and 2006 mainly in J Phys Chem B and Biophys.
> J.), we hope to obtain a quantitative approach to the absolute binding
> Gibbs energy from the integration of the Boltzmann factor for the pmf,
> but our problem is whether or not we should perform before in this
> curve the so-called entropic correction (also named by others volume
> correction term). The abovementioned paragraph is in the page 111 (the
> first page of chapter 6):
> 
>  
> 
> “When a distance between two atoms or the centers of mass of two
> groups is constrained or restrained, there will be a purely entropic
> contribution to the pmf due to the rotation of the two groups. For a
> system of two non-interacting masses the potential of mean force is:
> 
> Vpmf (r) = (nc-1)kBT log(r)           (6.1)
> 
> where nc is the number of dimensions in which the constraint works
> (i.e. nc = 3 for a normal constraint and nc = 1 when only the
> z-direction is constrained).”
> 
>  
> 
> I think that I understand the meaning and source of that term but the
> paragraph follows:
> 
>  
> 
> “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.”
> 
>  
> 
> I assume that our case is very similar to a substrate-protein complex
> and then we should not correct the pmf, but I do not understand
> exactly why not.
> 
>  
> 
>  
> 
> Angel Piñeiro.
> 
> 
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