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, 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. We demonstrate 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: it is likely to have a strong impact in Drug Design.
Supplementary materials
Title
Supplementary Information for: A Foundation Model for Accurate Atomistic Simulations in Drug Design
Description
Supplementary Information
Actions



![Author ORCID: We display the ORCID iD icon alongside authors names on our website to acknowledge that the ORCiD has been authenticated when entered by the user. To view the users ORCiD record click the icon. [opens in a new tab]](https://www.cambridge.org/engage/assets/public/coe/logo/orcid.png)