Premium
On the transferability of hydration‐parametrized continuum electrostatics models to solvated binding calculations
Author(s) -
Rankin Kathryn N.,
Sulea Traian,
Purisima Enrico O.
Publication year - 2003
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.10261
Subject(s) - transferability , electrostatics , chemistry , computational chemistry , electrostatic interaction , chemical physics , molecular dynamics , statistical physics , physics , computer science , machine learning , logit
Using molecular mechanics force field partial atomic charges, we show the nonuniqueness of the parametrization of continuum electrostatics models with respect to solute atomic radii and interior dielectric constant based on hydration (vacuum‐to‐water transfer) free energy data available for small molecules. Moreover, parameter sets that are optimal and equivalent for hydration free energy calculations lead to large variations of calculated absolute and relative electrostatic binding free energies. Hence, parametrization of solvation effects based on hydration data, although a necessary condition, is not sufficient to guarantee its transferability to the calculation of binding free energies in solution. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 954–962, 2003