UBio-MolFM: Enabling Biomolecular Dynamics at DFT Accuracy and $10^5$ Atoms with One Untuned Potential

Abstract

Ion conduction, membrane permeation and metal recognition hinge on electronic structure, yet first-principles simulation reaches only hundreds of atoms. UBio-MolFM lifts that ceiling: a foundation model trained on 160 million quantum-chemical labels, its receptive field spanning non-covalent distances at near-linear cost. The barrier is cost, not principle. One untuned potential keeps force error near 20 meV/Å past a thousand atoms, reproduces water's X-ray structure and ion hydration, and holds an RNA Mg$^{2+}$ site without ion-specific parameters. Cyclosporine A pays 3.5 kcal/mol in water for its permeable conformer, gated by one kinetically asymmetric hydrogen bond that a fixed-charge model flattens. In a 108,964-atom KcsA channel on one GPU, the relaxed four-ion column is anhydrous in all five replicas, in direct contact in four---the knock-on geometry ten fixed-charge simulations never form. It remains orders of magnitude costlier. Where electronic structure decides the answer, first-principles simulation is in reach.