Investigating Enzyme Function by Geometric Matching of Catalytic Motifs

Abstract The rapidly growing universe of predicted protein structures offers opportunities for data driven exploration but requires computationally scalable and interpretable tools (1–3) . We developed a method to detect catalytic features in protein structures, providing insights into enzyme function and mechanism. A library of 6780 3D coordinate sets describing enzyme catalytic sites, referred to as templates, has been collected from manually curated examples of 762 enzyme catalytic mechanisms described in the Mechanism and Catalytic Site Atlas (4–6) . For template searching we optimised the geometric-matching algorithm Jess (7) . We implemented RMSD and residue orientation filters to differentiate catalytically informative matches from spurious ones. We validated this approach on a non-redundant set of high quality experimental (n=3751,