have you evaluated the error bars on this curve?
On Tue, Jan 11, 2011 at 10:59 AM, Catein Catherine
<askamber23.hotmail.com>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
>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Tue Jan 11 2011 - 08:30:06 PST
