Abstrakt
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.