Schrodinger, Inc. proposes to expand the capabilities of the PS-GVB electronic structure package, a suite of programs for ab initio calculations on large biomolecular systems. The major features to be added are (i) accurate electron correlation methods, including gradient- corrected density functional theory and a synthesis of second order perturbation theory (PT) with generalized valence bond (GVB) methods; (ii) analytical gradients and second derivatives for Hartree-Fock, GVB, GVB-PT, and density functional calculations; (iii) a more robust and flexible user interface; and (iv) a reaction field method for computing solvation energies based on interfacing PS-GVB with a Poisson-Boltzmann solver. This diverse functionality, combined with the order-of-magnitude performance advantages inherent in our pseudospectral methodology, will allow PS-GVB to be used for a wide variety of important biological/biomedical applications. These include development of improved force fields for peptides and nucleic acids, calculation of interaction potentials for drug molecules interacting with proteins and nucleic acids, determination of activation barriers and reaction rates for enzymatic reactions, and evaluation of solvation energies for drug molecules.
