Beyond binding: designing molecules for biological function

Join us for the NYAGIM 2025 Q4 event, supported by Schrödinger, featuring Huafeng Xu from Atommap, to deliver a talk on computational drug discovery.

Abstract
Emerging therapeutic modalities—targeted protein degraders, biased agonists, allosteric modulators, and more—operate beyond occupancy-based inhibition, requiring molecules that not only bind but also reshape conformational landscapes of proteins and multi-protein complexes or induce non-native protein complexes to drive specific biological outcomes. Historically, such beyond-binding molecules have been discovered largely by serendipity. Today, advances in computational modeling of protein structures and dynamics, integrative structural biology, pharmacodynamic modeling, and high-resolution functional assays make it increasingly feasible to design molecules for their functional effects rather than binding affinities alone. I will present examples from targeted protein degradation, illustrating how integrated workflows combining multi-protein complex modeling, molecular design, and wet-lab feedback can yield potent, oncogene-specific degraders, while highlighting the challenges in predicting conformational dynamics and the kinetics of complex biological processes. I will also outline opportunities in designing biased agonists, conformation modulators, and kinetic modulators, pointing toward a new generation of small-molecule medicines engineered to reprogram biological function.

Event Details
Join the NYAGIM community to connect with peers from academia and industry working in in silico drug discovery. This is a great opportunity to exchange ideas, learn from leading experts, and be inspired.

• Format: In-person only (no remote attendance or recordings)
• RSVP Deadline: December 9, 2025

We look forward to seeing you there!