Professor Warshel's research covers a wide range of problems in modern biophysical chemistry. He and his coworkers have pioneered several of the most effective models for computer simulations of biological molecule. The studies of Warshel's group include the following:
Simulations of Enzyme Catalysis and Protein Action
Our early works paved the way for quantitative theoretical studies of enzymatic reactions. These works introduced the Hybrid - Quantum Mechanical / Molecular Mechanics (QM/MM) method and a microscopic approach for studies of electrostatic effects in proteins. The QM/MM and related approaches allow other scientists to study the energetics and dynamics of enzymatic reactions. Our group continues to push the frontiers of the field developing new approaches, studying complex effects such as quantum tunneling and entropic effects in enzymes and exploring the action of enzymes of special biological importance.q Simulating the Dynamics of Photobiological Processes
The first molecular dynamics simulation of a biological process was reported by Warshel in a 1976 study of the primary event of the vision process. Warshel's group continues to be very active in this field, studying ultrafast reactions such as the primary processes in the photosynthetic reaction center (where their theoretical study was the first to elucidate the correct electron transfer mechanisms) and the photoisomerization reaction in bacteriorhodopsin.
Simulation of Chemical Reactions in Solution
In order to understand enzymatic reactions it is crucial to have a quantitative picture of the corresponding reference reactions in solutions. The realization of this fact led Warshel's group to spend a major effort on studying the energetics and dynamics of chemical processes in solution. These studies include the use and development of various QM/MM approaches and related models for quantitative simulations of chemical reactions in solutions.
Electrostatic Energies in Macromolecules
Our early works involved the development of the first physically consistent models for studies of electrostatic energies in proteins. The use of these models led to the current realization that electrostatic energies provide the best way of correlating structure and function of biological molecules. The use of calculations of electrostatic energies in analyzing a wide range of biological problems is a major part of the research effort of Warshel's group. This includes evaluation of pKa's and redox potentials of proteins, drug designs, and studies of protein-protein interactions.
The simplified model for protein folding introduced by Levitt and Warshel is
now the method of choice in most studies of protein folding. Our recent effort
in this direction has focused on developing innovative ways of using the results
of the simplified model in the evaluation of the corrresponding free energies
of more detailed all-atom models.