【大师讲坛】第232期:Computational Exploration of Mechanisms of Catalysis by Novel Enzymes
In collaboration with the group of Yi Tang at UCLA, we have explored the use of Alfafold 2 and 3 protein folding predictions and QM and MD studies of mechanism and ligand binding to investigate how novel enzymes catalyze reactions. The Houk and Tang groups have studied a variety of enzymes that catalyze pericyclic reactions. These enzymes include well-studied enzymes such as chorismate mutase and a Diels-Alderase/[6+4]ase, SpnF. The former involves salt bridges, hydrogen-bonding, and pre-organization, while the latter involves primarily hydrophobic effects and preorganization. Two novel pericyclases discovered by the Tang group, BruB and Sdng, will be described here. The former involves a cascade of pericyclic reactions, while the latter involves covalent iminium catalysis. A new selective copper-dependent alkyl group chlorinase, ApnU, will also be discussed.
Kendall N. Houk
美国国家科学院院士、中国科学院外籍院士