Drug discovery is being pursued through computer-aided design, synthesis, biological assaying, and crystallography. Lead identification features <i>de novo</i> design with the ligand growing program <i>BOMB</i> or virtual screening by docking. Emphasis is placed on optimization of the resultant hits to yield potent, drug-like inhibitors. Monte Carlo/free-energy perturbation (FEP) simulations identify the most promising choices for substituents on rings, heterocycles, and linking groups. The illustrated applications center on inhibitor design for HIV-1 reverse transcriptase, JAK2 kinase, and SARS-CoV-2 main protease. Micromolar leads have been rapidly advanced to low nanomolar inhibitors, and numerous crystal structures for protein-inhibitor complexes have been obtained.

Efficient discovery of potent enzyme inhibitors using FEP guidance

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.