On Thu, 2014-09-18 at 16:07 +0300, Thomas Evangelidis wrote:
> On 18 September 2014 15:59, Jason Swails <jason.swails.gmail.com> wrote:
>
> > On Thu, 2014-09-18 at 15:15 +0300, Thomas Evangelidis wrote:
> > > >
> > > > MMPBSA.py never accounts for PBC. There is only one GB implementation
> > > > that I'm aware of that does (and I don't know how much sense such an
> > > > approach makes).
> > > >
> > > > You may want to look into the membrane capabilities of PBSA. It's
> > > > relatively new functionality, but it was designed for studies like this
> > > > (it treats the membrane and solvent implicitly by setting up multiple
> > > > dielectric regions).
> > > >
> > > >
> > > Thank you. I just had a look. I must define the membrane thickness and
> > the
> > > cylindrical exclusion region at the center of the protein. I have done
> > this
> > > in the past with APBS for individual protein models and I spent a lot of
> > > time for trial, error and visualization until I find the optimum values,
> > > which were still not perfect. I think I could avoid all this if I measure
> > > relative free energies of binding for the ligands I have as I would do
> > for
> > > a water soluble protein. Unless I am missing something, the terms
> > > accounting for solvation and desolvation of the transmembrane part of the
> > > protein with cancel out.
> >
> > Can you make a similar argument about cancellation of errors with
> > regards to not having periodic images of the membrane?
> >
> > I believe you are in uncharted waters here with MM/PBSA and MM/GBSA
> > analyses, so you will likely have to try and answer most of these
> > questions by trying stuff out.
> >
> >
> Does the same apply to alanine scanning to estimate the contribution of the
> mutated residue to ligand binding? Do you reckon the membrane slab is
> necessary for this type of calculation too?
The membrane slab, potentially. Having it replicated out to infinity in
every direction via periodicity, probably not. But I'm only
speculating.
--
Jason M. Swails
BioMaPS,
Rutgers University
Postdoctoral Researcher
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Received on Thu Sep 18 2014 - 06:30:05 PDT
