Calander Home 2001-2002 2002-2003 Jiali Gao Dynamics, pathways, and tunneling - a computational perspective of enzyme catalysis Date: September 16 Time: Noon to 1 Place: BSBE 4-101 A great challenge in molecular biology is to elucidate the enormous power of enzyme's ability to catalyze chemical reactions. This requires a detailed analysis of factors that may contribute to the lowering of the free energy of activation. These include protein dynamics, transition state stabilization and reactant state destabilization, solvation and desolvation, and quantum mechanical tunneling among other factors. In enzyme kinetics modeling, there are three main ways in which quantum mechanics should be included. First, the electronic structure of the reactant system must be treated quantum mechanically. Second, the discrete nature of quantum mechanical vibrational energies should be incorporated in the description of nuclear motion for computing the potential of mean force. Finally, quantum mechanical tunneling should be considered, particularly for reactions involving hydrogen transfer. I will use the proton transfer reaction catalyzed by methylamine dehydrogenase as an example to illustrate the necessity of including these quantum mechanical treatments to determine the free energy of activation and the significance of dynamics, tunneling, and barrier lowering factors on catalysis.