Polarizable Force Fields for Protein Simulations

Abstract

Computer simulations have become a widely used tool in biophysical and biochemical research. Fixed-charges empirical force fields have the advantage of computational speed, but explicit treatment of electrostatic polarization as a way to represent many-body interactions is often necessary if accurate energetic results are desired. Examples of such results include protein-ligand binding energies and acidity constants. We have demonstrated that using a polarizable force field permits achieving a ca. 0.6 pH units accuracy in calculating protein pKa values and qualitatively successful predictions of protein-ligand complex stabilities which are predicted as unstable by fixed-charges force fields. Moreover, we are developing a fast version of a complete polarizable force field for proteins, which is expected to speed up these accurate calculations by about an order of magnitude. Furthermore, the development of our polarizable force fields id greatly facilitated by extensive use of quantum mechanical data for both fitting and testing purposes.