Jean Philippe Piquemal

Laboratoire de Chimie Théorique, Sorbonne Université, 75005 Paris, France - Piquemal Group

A Quantum Foundation Model for Accurate Atomistic Simulations in Drug Design.

Abstract

While artificial intelligence has revolutionized the prediction of static protein structures, characterizing their dynamics and interactions with drug candidates remains a computational bottleneck. Here, we introduce FeNNix-Bio1 [1], a foundation machine learning model designed to power accurate, reactive atomistic simulations of biological systems at an unprecedented speed and scalability. Trained exclusively on synthetic quantum chemistry data, FeNNix-Bio1 accurately captures complex condensed-phase phenomena such as ion solvation and subtle liquid water properties for which it outperforms state-of-the-art specialized force fields. In this presentation, I will illustrate its versatility across a full spectrum of drug design applications, including the calculation of hydration free energies (HFEs), the reversible folding of small proteins, the simulation of protein-ligand absolute binding free energies and chemical reactions. Notably, FeNNix-Bio1 sets a new standard for the precise prediction of HFEs for the more than 600 molecules of the Freesolv dataset, providing sub-kcal/mol accuracy. By enabling scalable, quantum-accurate molecular dynamics without the need for manual parametrization, FeNNix-Bio1 bridges the gap between static structure prediction and dynamic biological reality.

References [1] A Foundation Model for Accurate Atomistic Simulations in Drug Design.T. Plé, O. Adjoua, A. Benali, E. Posenitskiy, C. Villot, L. Lagardère, J.-P.Piquemal, 2025, submitted, DOI: 10.26434/chemrxiv-2025-f1hgn-v4