We present a strategy for solvating biomolecules in molecular dynamics or M
onte Carlo simulations. The method employs a thin layer (often monomolecula
r) of explicit water with additional external forces representing the elect
rostatics, pressure, fluctuations, and dissipations caused by the neglected
bulk. Long-range electrostatic corrections are supplied through a set of v
ariable surface charges (polarons) that recreates the mean reaction field (
or dielectric properties) of an infinite solvent. We refer to this "fictiti
ous" boundary layer as a "surface of active polarons" (or SOAP). Test simul
ations of the solvation free energies of 15 amino acid analogs and nine ion
s are in good agreement with experiment (correlation coefficients: 0.995 an
d 1.000, respectively) despite the use of unaltered published force-fields
with only one adjustable parameter. Dynamical capabilities of SOAP are illu
strated by application to a six residue peptide with a stable conformation
(SYPFDV), as well as a flexible nine residue HIV-1 gp120 peptide (TLTSCNTSV
from PDB 1hhg). Future extensions, calibrations, and applications are disc
ussed briefly. (C) 2000 American Institute of Physics. [S0021-9606(00)51017
-4].