A NEW APPROACH TO ESTIMATION OF THE ELECTROSTATIC COMPONENT OF THE SOLVATION ENERGY IN MOLECULAR MECHANICS CALCULATIONS

A new approach (parametrized reaction-field multipoles (PRFM)) to modeling the effect of salvation in molecular mechanics calculations has been developed. This method is comparable in accuracy with finite-difference continuum models but requires a significantly shorter execution time. The induced charges, dipoles, and quadrupoles at the solute's atom centers are estimated employing a parametrized version of reaction field theory. The effective parametrization term allows computation of induced electrostatic multipoles in one iteration. The multipoles are positioned on the atoms' centers, which permits calculation of the required contributions to the solvation energy, electrostatic field, and Coulomb interaction of atoms at the same time. Results from pilot studies of small-molecule solvation energies, using the PARSE charges, are presented, which show good agreement with available experimental data. The additivity of the electrostatic contributions of atomic centers allows fast computation of the salvation term for molecules with partially fixed coordinates. This makes this model especially attractive for application to molecular docking.