W. Patrick Walters

This study uses cryo-EM to reveal structural plasticity and ligand promiscuity of CYP3A4, showing multiple conformations and highlighting the F/G loop's role in binding pocket remodeling.

The paper identifies data leakage in protein-ligand affinity benchmarks and proposes a new benchmark to evaluate true generalization.

The paper improves Thompson sampling for screening large chemical libraries by introducing a warmup routine and roulette wheel selection, achieving 100% recovery with 0.1% sampling.

Shape-based fragment merging (FrankenROCS) with Thompson sampling over 22 billion molecules found neutral SARS-CoV-2 macrodomain inhibitors; analogs reached single-digit micromolar IC50, backed by 137 crystal structures.

The paper evaluates computational hit-finding methods for targeting the WDR domain of LRRK2, a Parkinson's disease protein, finding that diverse strategies yielded weakly potent compounds.