Re: [AMBER] Is it an artifact for potential-of-mean force calculation?

From: Dmitry Nilov <>
Date: Tue, 11 Jan 2011 19:31:31 +0300

Which method do you use to obtain PMF?
The process of dissociation of a ligand has complex free energy
landscape and I think that it is really hard to define the way of
dissociation with the lowest barrier when calculating PMF. I suppose
that artifact of extremely high energy could relate to wrong
dissociation coordinate used in calculation.

On Tue, Jan 11, 2011 at 6:59 PM, Catein Catherine
<> wrote:
> Dear Sir/Madam,
> I am trying to study the Potential of mean force for a hydrophobic drug dissociate from a protein.  As the drug is buried deep inside a active site of the protein.  Large conformation change upon drug removal is expected.
> The PMF curves is found to be in the shape as follows:
> -                     -
>  -                  -
>   -                -
>    -     - - - - -
>     -  -
>       -
> ---> distance between drug and the receptor
> When I look at the structure, the min of the PMF represent the most favorable binding modes, i.e. when the drug bind into the active site, mainly through non-polar hydrophobic interactions.   The level off region after min is the transition period, i.e. from drug binding to drug removal process.  The high raise in PMF at the end of the curve is when the drug finally moved from the protein, whereas only long-distance or minor electrostatic interactions between the drug and protein residues remains.
> It is strange to found that the PMF raise up to a very high energy (as high as 100 kcal/mol) when the distance between drug and the receptor is very large.
> I am expecting if the interaction between the drug and receptor is weak (as the distance increase),  the PMF should become level off.
> Should we expect to see the PMF increase significantly?  If the drug is hydrophobic in nature, can I explain the large PMF (at large distance) as the hydrophobic drug is not favorable to go to the explicit solvent environment?  Could this attribute to PMF become as large as 100 kcal/mol?
> Would it be just an artifact at the end of PMF calculation?
> Best regards,
> Catherine
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Dmitry Nilov,
Lomonosov Moscow State University
AMBER mailing list
Received on Tue Jan 11 2011 - 09:00:02 PST
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