Hi Jason,
OK now I have some things to try. Thank you very much for your suggestions.
Regarding the dielectric boundary, because a set of nucleotides shares so
much similarity and because of the spacing between the ribose and phosphate
atoms by the c5' group, if it were technically possible to simply forget
this contribution to the dielectric boundary from neighbouring phosphate
atoms, and perform the main sum of energy contributions over only
non-phosphate atoms, I believe that this would produce valuable relative
binding free energy data. However I understand that within your
implementation, this may be very difficult to achieve.
Best regards,
Holly
On Wed, Dec 17, 2014 at 12:06 PM, Jason Swails <jason.swails.gmail.com>
wrote:
> On Wed, Dec 17, 2014 at 1:06 PM, Hallel Freedman <hfreedma.ualberta.ca>
> wrote:
> >
> > Hi Ray,
> > Thank you for your suggestion about changing the dielectric constant of
> the
> > solute. I will definitely try this.
> > Since I am interested in determining relative binding free energies,
> only,
> > for a set of nucleotides, I believe it may be justified to ignore the
> > contributions from the phosphate atoms since these belong to all ligands
> > whose binding free energies are being compared. So I was thinking in
> terms
> > of going into the AMBER MMPB-SA code and introducing a parameter, similar
> > to what you have with residue decomposition, where the sum over atomic
> > sites involved in determining binding free energy is only taken over
> > selected atoms. Does this sound feasible to you?
> >
>
> No. That's not how MM/PBSA works -- it parses the total energies computed
> for the whole system from sander (or NAB) output. In any case, the
> energies are not decomposable that way (deleting the phosphate group *also*
> modifies the dielectric boundary which in turn modifies the interactions
> between otherwise unrelated pairs of atoms; this is true for both GB and
> PB). [1] Apologies if it's clear that I'm misunderstanding what you are
> proposing here.
>
> Two more approximate things you could do is to zero-out the charges of the
> phosphate group (using the "change" command in ParmEd) or just strip those
> atoms out entirely. It may be a challenge to defend either approach,
> though, unless you can somehow quantify the error you are adding to your
> calculation by ignoring the phosphate electrostatics.
>
> Good luck,
> Jason
>
> [1] In GB, the "dielectric boundary" is wrapped into the effective GB
> radii, which is computed as an integral over nearby atoms, so it is also a
> non-local property that can't be decomposed.
>
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
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Received on Wed Dec 17 2014 - 11:30:03 PST
