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Re: WSN: hidrophobic/Van der Walls interactions energy... (fwd)
Sender: bruce_bush@merck.com (Bruce Bush)
Subject: Re: WSN: hidrophobic/Van der Walls interactions energy...
On Thu 29 Sep 1994, Rafael Szeinfeld wrote:
-------------------------------
>
> I don't agree with some of your ideas. You'll find my comments on
> it as the appear in your text.
>
> On Thu, 29 Sep 1994, Bruce Bush wrote:
> > There have been many arguments in the field of protein
> > folding over whether "polar" or "nonpolar" or "hydrophobic"
:::::>
> I agree with that.
> > The breakdown of energy of folding depends completely on how you
> > imagine the order of events. I believe therefore that such a breakdown
> > of energy into "contributions" is meaningless.
>
> I don't agree with that. The free energy change is due solely to
> ::::: (.. continued...)
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I thank Dr. Szeinfeld for his thoughtful reply and I will study it more
carefully. We probably agree on most aspects of the problem. Any apparent
disagreements may come from my misunderstanding of his query or perhaps
from something unclear in my answer.
We agree that it is possible to discuss the free energy change caused by any
single "mutation" or change to the solutes.
We agree that the most useful free energy changes to discuss are
the experimentally realistic ones where the solvent stays the same.
Two points that I probably did not state clearly, and would like to emphasize:
=> we cannot calculate "total" contributions to folding
=> energy (for all the hydrophobic groups, for example) by adding up the
=> individual contributions of mutating each hydrophobic group. <=
That is what I was trying to say by "order of events", but my examples
may have been confusing. I do not know any good way to define a "total"
contribution and I would welcome hearing a good definition.
=> simulated free energy changes (by Monte Carlo or molecular dynamics,
=> using thermodynamic integration or perturbation) along different "paths"
=> give different breakdown according to terms in the Hamiltonian,
=> such as nonbonded / bonded or polar / nonpolar. <=
Depending on the path chosen, one may attribute the different stabilities
of two mutant proteins entirely to the nonbonded interactions or entirely
to bondstretch and bend! So there will always be disagreement about
breakdowns of free energy if one compares different nonphysical paths.
Thank you again for the stimulating question and the thoughtful reply.
-- Bruce_bush@merck.com