Dear Jason,
Thank you for your kind reply. I know that it is impossible for me to
defend intdiel = 10. Actually I increased its value by 1 and I found that
around 10 it gives reasonable favourable free energy. I also found that
other important hydrophobic residues free energy increased at intdiel = 10
but they are in favourable region.
One more thing is that my protein is membrane protein so can I reduce
external dielectric constant? Or is there any way can I assign
transmembrane region low dielectric constant compare to remaining part?
I will also go for pair wise residue interaction energy.
Thanking you.
On Tue, Jun 12, 2012 at 4:55 PM, Jason Swails <jason.swails.gmail.com>wrote:
> I'm of the opinion that you should use 1. In the GB model, the 'internal'
> dielectric is actually the dielectric constant of the medium you transfer
> *from*, not really the internal dielectric constant of the protein. What I
> mean here is that, in GB, the solvation free energy is estimated by
> calculating the energy required to transfer the protein from vacuum/gas
> phase (where the dielectric constant is 1) into water (where the dielectric
> is 80). The dielectric constant of the protein itself actually cancels in
> the derivation.
>
> While there is some rationale to using intdiel != 1, the GB models were
> parametrized with intdiel=1 in mind, and I would suggest against deviating
> much from that value (in particular, values much higher than 2 are hard to
> defend). In particular, I think you would have a hard time defending the
> choice of intdiel=10 simply because it gives you answers you expect. You
> can use pairwise decomposition to analyze which specific residue-residue
> interactions give rise to your unexpected result, but I would be wary of
> damping out internal electrostatic interactions to get the behavior you
> expect.
>
> HTH,
> Jason
>
> On Tue, Jun 12, 2012 at 7:13 AM, Jignesh Patel <jbp087.gmail.com> wrote:
>
> > Hi,
> >
> > I have performed MD simulations of CCR2 with membrane (POPC). I have also
> > estimated per residue decomposition free energy using MM/GBSA method by
> > perl script. Residues which shows hydrophobic and hydrogen bond
> > interactions with ligand shows good decomposition free energy (about -8
> to
> > -2 kcal/mol). But, glutamic acid which shows ionic interaction with the
> > quaternary nitrogen of ligand gives unfavorable decomposition free energy
> > (about 8 kcal/mol). Here I kept external and internal dielectric constant
> > values 80 and 1 respectively. Then, internal dielectric constant was
> > changed to 10 which gave decomposition free energy of glutamic acid about
> > -2.5kcal/mol.
> >
> > Can anyone tell me what values should I use for internal dielectric
> > constant so I can get reasonable decomposition free energies for residues
> > showing both hydrophobic and ionic interactions?
> >
> > Thanks in advance.
> >
> > With regards,
> > Jignesh
> > _______________________________________________
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> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
>
>
>
> --
> Jason M. Swails
> Quantum Theory Project,
> University of Florida
> Ph.D. Candidate
> 352-392-4032
> _______________________________________________
> AMBER mailing list
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> http://lists.ambermd.org/mailman/listinfo/amber
>
--
With regards,
Jignesh Patel
JNU,
New Delhi
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Received on Tue Jun 12 2012 - 10:30:03 PDT
