Hi Jason,
Yes actually I put a large restraint (100kcal/mol) on the phosphate groups
during my simulations, which I am hoping should help in the cancellation of
error terms. If what I am suggesting is not a problem with the
implementation itself, then could you please point me to how to most easily
to modify the code for this?
My concern with stripping the phosphate atoms or changing their charges to
zero is that this would effectively place either a cavity or a hydrophobic
group within a very hydrophilic receptor pocket which may also introduce
large, this time positive, error terms to the binding free energies -
wouldn't you agree?
Thanks again,
Holly
On Wed, Dec 17, 2014 at 12:30 PM, Jason Swails <jason.swails.gmail.com>
wrote:
> On Wed, Dec 17, 2014 at 2:20 PM, Hallel Freedman <hfreedma.ualberta.ca>
> wrote:
> >
> > 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.
> >
>
> This isn't really an implementation detail. It's a property of solving
> the PB and GB equations themselves. They both depend on the physical shape
> of the molecule, and the shapes with and without the phosphate groups are
> different. If the phosphate was in exactly the same place for every
> ligand, then you will probably get a lot of the error to cancel when
> rank-ordering the different ligands, but I'm not sure how sensitive the PB
> energies will be to small changes in phosphate position and orientation.
>
> Ignoring the contribution of a set of atoms to the shape of the molecule
> (i.e., to the dielectric boundary) is a decision you have to make *before*
> you do the calculation -- it's not something you can simply post-process
> from the output regardless of the information that is printed. This is
> equivalent to the practice of stripping the phosphate groups with ParmEd or
> cpptraj (but then of course your net charge will be weird and probably not
> an integer).
>
> HTH,
> Jason
>
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
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Received on Wed Dec 17 2014 - 13:00:02 PST
