Reparametrization of the COSMO Solvent Model for Semiempirical Methods PM6 and PM7

An
accurate description of solvation effects is of high importance
in modeling biomolecular systems. Our main interest is to find an
accurate yet efficient solvation model for semiempirical quantum-mechanical
methods applicable to large protein–ligand complexes in the
context of computer-aided drug design. We present a survey of readily
available methods and a new reparametrization of the COSMO solvent
model for PM6 and PM7 calculations in MOPAC. We have tested the reparametrized
method on validation data sets of small drug-like molecules for which
experimental solvation free energies are available as well as on a
set of large model systems of the active site of carbonic anhydrase
II interacting with a series of ligands for which experimental affinity
values are known. In both cases, there is a significant improvement
in accuracy after the reparametrization and the addition of a nonpolar
term to the COSMO solvent model.