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

arXiv: https://arxiv.org/abs/2512.10034 · HTML: https://mlsanity.com/paper/2512.10034/

## Key facts

- Cited by 6 papers in the map (data through 14 Oct 2026).
- Builds on 15 of its 64 references that are in the map.
- First posted on arXiv 10 Dec 2025.

## Builds on (most cited first, 15 of 15)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [GPT-4 Technical Report](https://mlsanity.com/paper/2303.08774/) (2023)
- [The Llama 3 Herd of Models](https://mlsanity.com/paper/2407.21783/) (2024)
- [LLaMA: Open and Efficient Foundation Language Models](https://mlsanity.com/paper/2302.13971/) (2023)
- [Retrieval-Augmented Generation for Knowledge-Intensive NLP Tasks](https://mlsanity.com/paper/2005.11401/) (2020)
- [Reflexion: Language Agents with Verbal Reinforcement Learning](https://mlsanity.com/paper/2303.11366/) (2023)
- [Voyager: An Open-Ended Embodied Agent with Large Language Models](https://mlsanity.com/paper/2305.16291/) (2023)
- [ChemCrow: Augmenting large-language models with chemistry tools](https://mlsanity.com/paper/2304.05376/) (2023)
- [PaperQA: Retrieval-Augmented Generative Agent for Scientific Research](https://mlsanity.com/paper/2312.07559/) (2023)
- [Language agents achieve superhuman synthesis of scientific knowledge](https://mlsanity.com/paper/2409.13740/) (2024)
- [El Agente: An Autonomous Agent for Quantum Chemistry](https://mlsanity.com/paper/2505.02484/) (2025)
- [Aviary: training language agents on challenging scientific tasks](https://mlsanity.com/paper/2412.21154/) (2024)
- [MDCrow: Automating Molecular Dynamics Workflows with Large Language Models](https://mlsanity.com/paper/2502.09565/) (2025)
- [Automating MD simulations for Proteins using Large language Models: NAMD-Agent](https://mlsanity.com/paper/2507.07887/) (2025)

## Built on by (most cited first, 6 of 6)

- [El Agente Quntur: A research collaborator agent for quantum chemistry](https://mlsanity.com/paper/2602.04850/) (2026)
- [PolyJarvis: An LLM-Orchestrated Agent for Automated All-Atom Molecular Dynamics of Amorphous Homopolymers](https://mlsanity.com/paper/2604.02537/) (2026)
- [MDGYM: Benchmarking AI Agents on Molecular Simulations](https://mlsanity.com/paper/2605.08941/) (2026)
- [Auto-Configuring Scientific Simulators with Lightweight Coding-Agent Adapters](https://mlsanity.com/paper/2606.09774/) (2026)
- [MDArena: Evaluating Coding Agents on Realistic Molecular Dynamics Workflows](https://mlsanity.com/paper/2608.02642/) (2026)
- [Science Done on a Machine by a Machine: AI Agents in Computational Chemistry](https://mlsanity.com/paper/2608.18508/) (2026)

## Abstract (arXiv)

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.