Harold Scheraga, Cornell University: “Use of DFT Calculations of 13Cα Chemical Shifts for Validating, Refining, and Computing Protein Structure in Solution”

Apr 24 2009, 3:00 pm
Distinguished Lecture Series Guest Speaker: 

Harold Scheraga

George W. and Grace L. Todd Professor of Chemistry, Emeritus
Baker Laboratory of Chemistry and Chemical Biology
Cornell University

Date & Time: 
Friday, April 24, 2009, 3:00PM
Location: 
IBB, Suddath Room 1128
Host: 
Jeffrey Skolnick
Abstract: 
The 13Cα nucleus is a unique species for NMR studies of proteins, and its chemical shift provides important information for protein structure evaluation. The observed 13Cα chemical shift of a given amino acid residue reflects an ensemble of conformations of a whole protein. By use of DFT calculations of the 13Cα chemical shift for every residue in every conformation of an ensemble, it is possible to evaluate the quality of the ensemble and, if the quality is low, to refine the conformational ensemble. It is also possible to use the 13Cα chemical shifts to determine protein structure in solution. The DFT calculations of 13Cα chemical shifts, and their use for validating, refining, and computing protein structure in solution, will be discussed.
Additional Info: 

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.

Both experimental and theoretical methods are used in this research. The experimental work involves 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. 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, and enzyme-substrate complexes.

Much of the experimental and theoretical work involves the determination of the pathways of folding of proteins, and the mechanism of action of thrombin on fibrinogen (an important reaction in the blood clotting process).
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