Subject: electrostatic solvation energy of biomolecules

From: "S. Roy Kimura" <[email-masked]>
Date: Sun, 15 Mar 1998 15:26:48 -0500 (EST)

Dear CCLers,

I have a question regarding electrostatic calculations in proteins
relating to issues such as solvation, salt-bridge stability, or
binding energies. I have read that different workers have had varying
success in calculating electrostatic energies using the
Finite-Difference Poisson-Boltzman method. However, this method
suffers from the ambiguity of the dielectric constant of the protein
interior which, strictly speaking, shouldn't be considered a
homogeneous dielectric continuum in the first place.

I was wondering if anyone has made any progress in electrostatic
calculations by the full inclusion of solute motion, for instance by
conducting molecular dynamics or all-atom Monte Carlo simulations. I
realize that such a method will still neglect electronic polarization
but will at least correctly treat the inhomogeneity of the protein
interior, if it is possible to run long enough to adequately sample
the full electrostatic response. Moreover, I was thinking that
electronic polarization may still have a chance to be described by a
dielectric constant (eps = 2 to 4) superimposed on top of the explicit
solute motion which takes care of reorientational polarization.

I would appreciate if anyone could point me to some papers that
considers electrostatic calculations by averaging the response in MD
or MC simulations. I am interested specifically in the feasibility of
such calculations which must include solvent in some form (either
explicitly or implicitly). 

I have read some of the works by Warshel, Aqvist, and King who seem to
have ideas along this line; however, they chose to describe the solute
and solvent through a set of variable dipoles on a grid. I am
interested in knowing if it is possible to capture reorientational
polarization through explicit consideration of solute atom motion.

Thank you very much.

S. Roy Kimura
Molecular Engineering Research Laboratory
Department of Biomedical Engineering           email: [email-masked]
Boston Univesrity                              phone: (617)353-4726