Molecular modeling incorporating relaxed catalytic geometry

In our initial phase of simulations, reported in Q9 report, we focused on designed enzymes that perfectly recapitulated the geometry of the oleate hydratase active site. In order to broaden our search to catalytic geometries not observed in nature, we added additional allowed conformations to the ligand placement in the matching simulations. Previous simulations had delivered ~8,000 matches on a scaffold set of 207 proteins, while loosened catalytic constraints provided up ~60,000 matches. Significant computational time is required to evaluate the predicted energies of this second round of designs before manual filtering and curation can begin, and is currently in progress.