Harold A. Scheraga
George W. and Grace L. Todd Professor of Chemistry, Emeritus
Baker Laboratory of Chemistry and Chemical Biology
Ithaca NY 14853-1301
We are investigating the interactions that (a) dictate the folding of a polypeptide chain in water into the three-dimensional structure of a native protein and (b) determine the reactivity of such a protein molecule (e.g., as an enzyme) with other small and large molecules.
Previously, experimental and theoretical methods were used in this research, but the current research is confined to the theoretical approach. The experimental work involved genetic engineering and hydrodynamic (e.g., sedimentation and viscosity), spectroscopic (Raman, infrared, fluorescence, nuclear magnetic resonance, electron spin resonance, ultraviolet absorption, circular dichroism, and optical rotatory dispersion), immunochemical, and other physicochemical measurements on proteins, synthetic polymers of amino acids, and model compounds, in studies of the pathways of protein folding, and the mechanism of action of thrombin on fibrinogen (an important reaction in the blood clotting process. The theoretical work involves statistical mechanical studies of aqueous solutions of amino acids and peptides, and of conformational changes in proteins and polypeptides, and empirical energy calculations to determine the stable conformations of proteins, polypeptides, enzyme-substrate complexes, protein-protein interactions, nucleic acids, protein-nucleic acid interactions, and the pathways and thermodynamics of folding of proteins. The simulations involve massively parallel software development and massively parallel computing (with more than 1000 cores).