ORGN 3 |
| Stephen Benkovic, Department of Chemistry, Department of Chemistry, The Pennsylvania State University, 414 Wartik Laboratory, University Park, PA 16802 |
| With dihydrofolate reductases as a paradigm because of the wealth of structural and kinetic data available for wild-type and mutant forms of the enzymes, we have examined the question of the importance of conformational changes and their contributions to catalysis. We have supplemented kinetic and thermodynamic data with a direct study of the conformational fluctuations at the amide backbone of various enzyme complexes using dynamic NMR measurements (Wright and Dyson). Residues that exhibit high frequency motions both within and outside the active site influence the key rate constants that describe turnover. Molecular dynamic simulations (Brooks) reveal the existence of ground state correlated motions between the same residues. Mixed quantum, real time molecular dynamic simulations (Hammes-Schiffer), implicate a network of coupled motions arising in a series of thermally equilibrated enzyme conformations that act along the reaction-coordinate to optimize the reacting centers of the substrate and cofactor for chemical transformation. |
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James Flack Norris Award in Physical Organic Chemistry
8:35 AM-12:00 PM, Sunday, March 28, 2004 Anaheim Convention Center -- Bllrm A/B, Oral
Division of Organic Chemistry |