DynaMate: An Autonomous Agent for Protein-Ligand Molecular Dynamics Simulations

TL;DR

DynaMate is an autonomous multi-agent framework that automates the entire protein-ligand molecular dynamics simulation process, including setup, execution, and analysis, thereby reducing technical barriers and increasing efficiency in biomolecular research.

Contribution

It introduces a modular multi-agent system capable of autonomously designing, executing, and analyzing MD workflows for proteins and ligands, integrating dynamic tool use and self-correction.

Findings

Successfully automated 12 benchmark MD systems.

Achieved high success rate and efficiency in simulations.

Produced meaningful protein-ligand interaction analyses.

Abstract

Force field-based molecular dynamics (MD) simulations are indispensable for probing the structure, dynamics, and functions of biomolecular systems, including proteins and protein-ligand complexes. Despite their broad utility in drug discovery and protein engineering, the technical complexity of MD setup, encompassing parameterization, input preparation, and software configuration, remains a major barrier for widespread and efficient usage. Agentic LLMs have demonstrated their capacity to autonomously execute multi-step scientific processes, and to date, they have not successfully been used to automate protein-ligand MD workflows. Here, we present DynaMate, a modular multi-agent framework that autonomously designs and executes complete MD workflows for both protein and protein-ligand systems, and offers free energy binding affinity calculations with the MM/PB(GB)SA method. The framework integrates dynamic tool use, web search, PaperQA, and a self-correcting behavior. DynaMate comprises three specialized modules, interacting to plan the experiment, perform the simulation, and analyze the results. We evaluated its performance across twelve benchmark systems of varying complexity, assessing success rate, efficiency, and adaptability. DynaMate reliably performed full MD simulations, corrected runtime errors through iterative reasoning, and produced meaningful analyses of protein-ligand interactions. This automated framework paves the way toward standardized, scalable, and time-efficient molecular modeling pipelines for future biomolecular and drug design applications.