Secondary Binding\nSite of CYP17A1 in Enhanced Sampling\nSimulations

Androgens like testosterone and dihydrotestosterone play\na key\nrole in prostate cancer progression, making the enzyme CYP17A1, essential\nfor androgen synthesis, a crucial therapeutic target. Recent studies\nhave revealed electron density at the substrate entry channel, suggesting\nthe presence of a secondary binding site. In this study, we calculated\nthe binding free energy landscape of known ligands at this site using\nFunnel Metadynamics. Our results characterize this binding site and\nindicate that nonheme-interacting ligands could effectively bind to\nCYP17A1, providing a novel approach to the design of CYP17A1 inhibitors.