Dr. Ravi Radhakrishnan New York University Courant Institute of Mathematical Sciences
"Rare Event Processes in Physico-chemical & Biological Systems
Many physico-chemical processes such as nucleation events in phase transitions, conformational changes of biomolecules, and chemical reactions such as heterogeneous catalysis and enzymatic reactions are activated processes that involve rare transitions between stable or metastable basins in the free energy surface. Gaining a mechanistic perspective on such processes and predicting their rates continue to pose a daunting theoretical challenge.
In my talk, I will outline many theoretical developments to study activated processes in the context of phase transitions and nucleation in inhomogeneous systems, heterogeneous catalysis, and conformational transitions in biomolecular systems.
I will focus on my molecular simulation studies of the conformational changes in the mammalian DNA polymerase, pol beta, that direct the enzyme to an active state, i.e., one ready for catalyzing the nucleotide incorporation reaction. These studies on such a complex system were made possible by a combination of different simulation techniques that represent the state-of-the-art in biomolecular simulations. Our studies together with kinetic efficiency and fidelity measurements performed at NIH reveal key protein residues, mechanisms, and interactions that direct the enzyme to a reaction competent state in a substrate-sensitive manner. Together, they provide an atomic view into the enzyme kinetic pathways that bridge static structures from X-ray crystallography and NMR and macroscopic kinetic measurements, thereby suggesting crucial control mechanisms that have major implications on the fidelity and the efficiency of the polymerase.
BRIEF ACADEMIC/EMPLOYMENT HISTORY:
B. Tech, Indian Institute of technology, Madras, chemical engineering, 1995.
PhD, Cornell, chemical engineering, 2001. A study of phase transitions in lower-dimensional systems using molecular simulations and experiment.
Postdoctoral Associate with Bernhard Trout, MIT, chemical engineering, 2000-2002.
Postdoctoral Associate with Tamar Schlick, Dept. of Chemistry and Courant Institute, NYU, since 2003.