AMBER Archive (2008)

Subject: Re: AMBER: mm_pbsa positive ELE

From: Ray Luo (rluo_at_uci.edu)
Date: Mon Mar 17 2008 - 15:14:57 CDT

Qi,

My point was that this is physical... there is nothing wrong with
your observation.

However, a previous publication from the Kollman group set the
protein dielectric constant as high as 4 for charged binding sites.
Use of a higher dielectric constant in these calculations is to
effectively account for the limited sampling of dielectric responses
in the MD simulations. You can consult Warshel's many reviews on the
meaning of protein dielectric constants.

Best,
Ray

On Mar 17, 2008, at 12:23 PM, Qi Yan wrote:

> Hi,Ray:
>
> Thank you for your response. If it is like you said, what I can do?
> Does it mean I can not use mm_pbsa to calculate binding affinity?
>
> Thnaks,
>
> Qi
>
>
> -----Original Message-----
> From: owner-amber_at_scripps.edu on behalf of Ray Luo
> Sent: Mon 3/17/2008 1:33 PM
> To: amber_at_scripps.edu
> Subject: Re: AMBER: mm_pbsa positive ELE
>
> Qi,
>
> If you happen to have a situation where ligand binding causes the
> burial of a charge, then you may have a positive electrostatic
> contribution to binding free energy, i.e. desolvation of charge is
> not favorable.
>
> All the best,
> Ray
>
> On Mar 17, 2008, at 11:20 AM, Qi Yan wrote:
>
> > Hi,all
> >
> > I'm trying to calculate the binding affinity of a complex and its
> > mutants (I got three mutants. Each of them just change some residue
> > types which are in biding site). For these mutants, the results of
> > mm_pbsa seem reasonable, but, for the wild complex, the final ELE
> > value is positive (final ELE = com-rec-lig). Actually, these ELE
> > values of individual complex, receptor and ligand look normal. I
> > don't know whether the non-zero net charge can influence the
> > results. I choose "Dielectricity constant = 2.0" for all cases.
> > Does anybody can point me out?
> >
> > Thanks in advance,
> >
> > Qi Yan
> >
>
>
>

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