An important question in drug discovery is whether one can reprogram the substrate preference and activity of an enzyme rather than completely inhibiting its catalytic activity. Substrate-selective modulation could represent a paradigm shift in how we target diseases such as diabetes, Alzheimer’s and heart disease. The Denard Lab is developing high-throughput functional screens and statistical machine learning approaches to concurrently map enzyme distal regulation, discover and ultimately predict properties of ligand that elicit, induce, and stabilize substrate-selective conformations.
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