MDForge: Agentic Molecular Dynamics Pipeline Design under Sparse Simulator Feedback

Abstract:Molecular dynamics (MD) is the canonical in-silico method for atomistic molecular science, simulating molecular behavior from first-principle physics. Designing an MD pipeline for a new system requires substantial expert knowledge: running it on even one molecule is expensive, ruling out trial-and-error. We automate this expert pipeline-design process with an LLM agent. Unlike existing MD agents that orchestrate a predefined tool set, we treat pipeline design as open-ended code generation in which the agent's behavior is reshaped online by verbal reward. Specifically, we build MDForge, an LLM agent whose in-context update rule densifies the sparse reward via a multi-agent debate among physics experts. On three SAMPL host-guest binding free-energy benchmarks, MDForge automatically designs MD pipelines competitive with human experts. Deployed on a library of unseen candidate guests, its CB[7] pipeline discovers a novel binder that wet-lab competition NMR confirms is a high-affinity, picomolar CB[7] binder. Our data and code are available at this https URL.

Artificial Intelligence (cs.AI); Computation and Language (cs.CL); Machine Learning (cs.LG)

arXiv:2606.12916 [cs.AI]

(or arXiv:2606.12916v1 [cs.AI] for this version)

https://doi.org/10.48550/arXiv.2606.12916 Focus to learn more arXiv-issued DOI via DataCite (pending registration)

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