A Foundation Model for Accurate Atomistic Simulations in Drug Design

17 December 2025, Version 4
This content is an early or alternative research output and has not been peer-reviewed by Cambridge University Press at the time of posting.

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.

Keywords

Foundation machine learning model
molecular dynamics
drug design

Supplementary materials

Title
Description
Actions
Title
Supplementary Information for: A Foundation Model for Accurate Atomistic Simulations in Drug Design
Description
Supplementary Information
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting and Discussion Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.