GPU infrastructure for ML/MM with electrostatic embedding for enzyme chemistry
Venkat Kapil
Abstract
We present a fully GPU-native framework for machine learning/molecular mechanics (ML/MM) enhanced sampling simulations with electrostatic embedding, demonstrated on an enzymatic reaction. The framework combines a JAX port of the pretrained MACE-POLAR-1-M model, an electrostatic embedding scheme compatible with the MACE-POLAR architecture, and integration with JAX-MD and PLUMED-JAX for end-to-end compiled enhanced sampling. The implementation is developed using GPT-6.1-Sol within Codex, with reasoning effort set to high. Using replica exchange umbrella sampling, we calculate the free energy profile of nucleophilic substitution in haloalkane dehalogenase in approximately 200 H100 GPU hours, treating the entire protein and reactants with MACE-POLAR-1-M-JAX and most of the solvent with molecular mechanics.
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