From: Wei Chen (gtg553p_at_mail.gatech.edu)
Date: Thu May 12 2005 - 11:19:48 CDT
Hi, Phil,
Thanks!
You know, electrostatic force is dominant one for dG.
So it is always a problem to calculate it accurately.
Wei Chen
ÒýÓÃ Philip Fowler <philip.fowler_at_ucl.ac.uk>:
> I know that people have introduced an ion and scaled that by lambda also to
> maintain neutrality.
>
> I think this is a bit of a moot point as the main reason for maintaining
> neutrality is if one is using PME which only converges with a neutral system.
>
> But charged MD sims are stable, so I am not sure.
>
> I have run a E2I mutation and did not introduce a charge. The result was
> horrible but that may have been because the mutation was too complex (we were
>
> also mutating a second amino) rather than because of the charge. It certainly
>
> does mean that if the residue is solvent exposed in one system and buried in
>
> the other you will see large dG's as the water rearranges.
>
> Hope this helps.
>
> --Phil
>
> > The charge is a problem. So far, I didn't deal with ions.
> > Do you have any idea?
> >
> > Wei
> >
> > Quoting Philip Fowler <p.w.fowler_at_qmul.ac.uk>:
> > > We have also been using the FEP module with NAMD2.5 and agree that a
> > > soft-core
> > > potential would help enormously. I am also interested in the possibility
> > > that it may allow one to assess when a lambda simulation has "relaxed" -
> > > I hestitate to say equilibrated (Yang et al. J Chem Phys 120 2618
> > > (2004)).
> > >
> > > At UCL we have briefly looked at implementing it, but currently do not
> > > have anyone free to do it. Is anyone on the list implementing it (or
> > > would be tempted to give it a go?).
> > >
> > > Wei - are you introducing a charge into your system, and if so, how are
> > > you dealing with this (e.g. scaling an ion also)?
> > >
> > > --Phil Fowler
> > >
> > > > There is, indeed, a singularity when lambda tends towards
> > > > 0 or 1 with growing particles - known as "end-point"
> > > > catastrophe. One way to circumvent this difficulty is to
> > > > use a soft-core potential in the spirit of Beutler et al.
> > > > Chem. Phys. Lett. 1994, 222, 529-539. Unfortunately, we
> > > > have not implemented it yet in NAMD. A work-around that you
> > > > might want to try is to use windows of uneven width, getting
> > > > infinitesimal as you approach the end points of the reaction
> > > > path. In addition, you may want to equilibrate and start at
> > > > lambda = 0.5, and move in both directions, towards 0 and 1,
> > > > to avoid poor vdW contacts due to growing atoms (note that,
> > > > strictly speaking, in the dual-topology paradigm, we scale
> > > > the interaction potential energy with lambda rather than the
> > > > non-bonded parameters of the appearing/disappearing side chains).
> > > >
> > > > Chris Chipot
> > > >
> > > > Wei Chen wrote:
> > > > >Hi, all,
> > > > >
> > > > >Now I am using free energy perturbation to calculate free energy
> > > > > difference. The system is one ligand + one receptor. I want to
> mutate
> > > > > one residue in binding pocket from Glycine to Aspartate.
> > > > >
> > > > >Basically, I grow aspartate and shrink glycine at the same time.
> > > > >The problem is that aspartate could overlap with other residues due
> > > > >to its bigger size than glycine. So the VDW energy becomes very
> large,
> > > > >even infinite. Anybody has ideas to deal with this situation?
> > > > >
> > > > >Thanks!
> > > > >
> > > > >Wei Chen
> > > >
> > > >
> _______________________________________________________________________
> > > >
> > > > Chris Chipot, Ph.D.
> > > > Equipe de dynamique des assemblages membranaires
> > > > Unité mixte de recherche CNRS/UHP No 7565
> > > > Université Henri Poincaré - Nancy 1 Phone: (33)
> > > > 3-83-68-40-97 B.P. 239 Fax:
> (33)
> > > > 3-83-68-43-87 54506 Vandoeuvre-lès-Nancy Cedex
> > > > E-mail:
> Christophe.Chipot_at_edam.uhp-nancy.fr
> > > >
> http://www.edam.uhp-nancy.fr
> > > >
> > > > To sin by silence when we should protest makes cowards out of
> men
> > > > Ella Wheeler
> Wilcox
> > > >
> _______________________________________________________________________
> > >
> > > --
> > > Philip Fowler,
> > > PhD Student
> > > Centre for Computational Science,
> > > UCL Chemistry
> >
> > --
>
> --
> Philip Fowler,
> PhD Student
> Centre for Computational Science,
> UCL Chemistry
>
--
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