Translational enzymology and drug discovery

A comprehensive understanding of enzyme structure-function relationships has historically been fruitful in identifying novel targets and in rational drug design. The rapid development of methods for protein structure prediction and determination, together with the exponential growth in genomic information, presents an unprecedented opportunity to explore complex enzymatic reactions and protein dynamics with the goal of obtaining bioactive molecules that can interfere with cellular function for treating disease. We use mechanistic metalloenzymology, structural biology, biophysical tools, and genome mining to investigate how enzymes in nature utilize metallocofactors and protein dynamics to facilitate challenging biochemical conversions. By decoding the “language” used by enzymes in catalysis, we hope to deliver novel tools and strategies for innovative drug discovery.