Faculty Research Interest

Theoretical Studies of Biophysical Systems, Quantum Mechanics, and Statistical Mechanics

Faculty Record

The research in my group has three broad aims. First we wish to develop approximate methods that allow the practical prediction of the dynamics of chemical reactions in biomolecular systems. Because even in large biological systems, many events are governed by quantum mechanics, we seek to develop methods that allow the study quantum processes in complex systems. In biological systems, some enzymatic reactions, which involve the transfer of a hydrogen atom, seem to proceed almost entirely by quantum mechanical tunneling. Our research has focused on the use of Feynman Path Integrals to study these complex systems. Using such approaches we have uncovered the extraordinary possibility that in certain enzyme systems, evolution has developed a catalyst that maximizes quantum tunneling by making a barrier to reaction thinner, rather than the conventional view that enzymes always work to make barriers to reaction smaller. This concept of directed protein motions, which we have termed promoting vibrations, is now an area of international research focus.

The second aim of my work is to combine computer-learning algorithms with quantum chemical calculations. We focus on the problem of rational drug design, and inhibitor recognition by enzymes, transporters, and receptors. Some of our research focuses on the design of transition state inhibitors. Our collaborator V. Schramm at AECOM has shown that drugs that mimic the transition state, a point midway in the transformation from reactants to products, provide a highly efficient way to stop an undesired biochemical process. This was one of the first applications of artificial intelligence to rational drug design. Diseases to which we apply this methodology include trypanosome infections, cholera, and types of cancers.

The third aim of research in my group is to develop methods that will allow us to understand the basic dynamics of condensed phases. In particular, we seek to understand how liquids behave, how they influence chemical reaction, and finally how these effects are made manifest in biological systems.