Research Interests

Bill's research interests are broad including organic, physical, and biochemistry. He has been a pioneer of computational studies of organic and biomolecular systems in solution. This has included development and application of (1) the widely used OPLS force fields including the TIPnP models for water, (2) free-energy methods for organic reactions, host-guest binding and other equilibria, (3) mixed quantum and molecular mechanics (QM/MM) simulations for organic and enzymatic reactions in solution, and (4) methods for computer-aided molecular design, especially for enzyme inhibitors. His development of the OPLS force fields and TIPnP water models facilitated widespread modeling of biomolecular systems in aqueous solution starting in the 1980s. His prolific development of molecular modeling software (BOSS, MCPRO, BOMB) has been essential to the technical advances. Bill's research on protein-ligand binding has evolved to de novo drug design and synthesis, particularly for anti-infective, anti-proliferative, and anti-inflammatory agents. His computer-guided methods have led to the rational design and discovery of extraordinarily potent anti-HIV agents, an antibacterial agent that has completed phase-II clinical trials, and a first-in-class anti-inflammatory agent that is in late preclinical development.

Membership Type


Election Year


Primary Section

Section 14: Chemistry

Secondary Section

Section 29: Biophysics and Computational Biology