Generalized Born Solvent Question

From: Aron Broom (broomsday_at_gmail.com)
Date: Thu Jul 19 2012 - 13:34:34 CDT

Hi Everyone,

I've asked before about the SASA term with GBIS simulations, but I'm still
slightly confused and have what I think is a rather quick question:

So I understand that in a GBIS simulation without SASA, the lack of
potential VDW interactions between water and say a hydrophobic sidechain,
means that the sidechain will tend to favour interacting with the protein,
thereby giving a partial hydrophobic effect. Moreover, when one adds in
the SASA term, the energy gradients tend to favour burial of exposed
surfaces, ideally, recapitulating in full the hydrophobic effect. What I
don't understand, is that in my reading of the articles presenting these
methods, I don't see anything about the polarity of the atoms being taken
into account for this SASA term. To me, this would suggest that a solvent
accessible polar group is just as unfavourable as a similarly exposed
hydrophobic group as far as SASA is concerned. Furthermore, because
enthalpic interactions between polar groups are stronger than between
hydrophobic groups, this would imply that if one ran a GBIS + SASA
simulation of a protein for long enough, you'd end up with a "native state"
in which the polar groups were all buried in the core.

There must be something critical I'm missing here?

~Aron

-- 
Aron Broom M.Sc
PhD Student
Department of Chemistry
University of Waterloo

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