S115: Engineering Hyper-catalytic Enzymes through Conformational Modulation

Enzymes are phenomenal catalysts. Engineered enzymes that provide enhanced reaction rates are widely desired. However, the current understanding of underlying factors that control enzyme efficiency remains a mystery. Our joint computational-experimental efforts are providing new insights that indicate that enzyme structure encodes dynamics while structure-dynamics encode function. Moreover, the surrounding solvent plays a critical role by thermo-dynamical coupling with the reaction. Using these fundamental insights, we have designed an enzyme engineering approach that manipulates enzyme conformations to achieve enhanced activity. Computational results from a number of enzyme systems indicating the role of internal dynamics in catalysis will be presented. Further, our approach for experimental engineering and the results from lipase B from Candida antarctica, which shows about 30 fold improvement in catalysis over wild type enzyme will also be presented.