# MDForge: Agentic Molecular Dynamics Pipeline Design under Sparse Simulator Feedback

arXiv: https://arxiv.org/abs/2606.12916 · HTML: https://mlsanity.com/paper/2606.12916/

## Key facts

- Cited by 2 papers in the map (data through 14 Oct 2026).
- Placed in Medical and scientific domain agents, one of 16 directions in LLM agents and tool use.
- Builds on 60 of its 111 references that are in the map.
- First posted on arXiv 11 Jun 2026.

## Placed in

- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)

## Builds on (most cited first, 30 of 60)

- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [Proximal Policy Optimization Algorithms](https://mlsanity.com/paper/1707.06347/) (2017)
- [Training Verifiers to Solve Math Word Problems](https://mlsanity.com/paper/2110.14168/) (2021)
- [ReAct: Synergizing Reasoning and Acting in Language Models](https://mlsanity.com/paper/2210.03629/) (2022)
- [Judging LLM-as-a-Judge with MT-Bench and Chatbot Arena](https://mlsanity.com/paper/2306.05685/) (2023)
- [DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learning](https://mlsanity.com/paper/2501.12948/) (2025)
- [Reflexion: Language Agents with Verbal Reinforcement Learning](https://mlsanity.com/paper/2303.11366/) (2023)
- [Deep reinforcement learning from human preferences](https://mlsanity.com/paper/1706.03741/) (2017)
- [Let's Verify Step by Step](https://mlsanity.com/paper/2305.20050/) (2023)
- [Self-Refine: Iterative Refinement with Self-Feedback](https://mlsanity.com/paper/2303.17651/) (2023)
- [Constitutional AI: Harmlessness from AI Feedback](https://mlsanity.com/paper/2212.08073/) (2022)
- [AutoGen: Enabling Next-Gen LLM Applications via Multi-Agent Conversation](https://mlsanity.com/paper/2308.08155/) (2023)
- [Improving Factuality and Reasoning in Language Models through Multiagent Debate](https://mlsanity.com/paper/2305.14325/) (2023)
- [Decision Transformer: Reinforcement Learning via Sequence Modeling](https://mlsanity.com/paper/2106.01345/) (2021)
- [CAMEL: Communicative Agents for "Mind" Exploration of Large Language Model Society](https://mlsanity.com/paper/2303.17760/) (2023)
- [Curiosity-driven Exploration by Self-supervised Prediction](https://mlsanity.com/paper/1705.05363/) (2017)
- [Hindsight Experience Replay](https://mlsanity.com/paper/1707.01495/) (2017)
- [The AI Scientist: Towards Fully Automated Open-Ended Scientific Discovery](https://mlsanity.com/paper/2408.06292/) (2024)
- [MoleculeNet: A Benchmark for Molecular Machine Learning](https://mlsanity.com/paper/1703.00564/) (2017)
- [Encouraging Divergent Thinking in Large Language Models through Multi-Agent Debate](https://mlsanity.com/paper/2305.19118/) (2023)
- [Exploration by Random Network Distillation](https://mlsanity.com/paper/1810.12894/) (2018)
- [Math-Shepherd: Verify and Reinforce LLMs Step-by-step without Human Annotations](https://mlsanity.com/paper/2312.08935/) (2023)
- [ChatDev: Communicative Agents for Software Development](https://mlsanity.com/paper/2307.07924/) (2023)
- [Solving math word problems with process- and outcome-based feedback](https://mlsanity.com/paper/2211.14275/) (2022)
- [ExpeL: LLM Agents Are Experiential Learners](https://mlsanity.com/paper/2308.10144/) (2023)
- [ChemCrow: Augmenting large-language models with chemistry tools](https://mlsanity.com/paper/2304.05376/) (2023)
- [RLAIF vs. RLHF: Scaling Reinforcement Learning from Human Feedback with AI Feedback](https://mlsanity.com/paper/2309.00267/) (2023)
- [Linear Transformers Are Secretly Fast Weight Programmers](https://mlsanity.com/paper/2102.11174/) (2021)
- [MLE-bench: Evaluating Machine Learning Agents on Machine Learning Engineering](https://mlsanity.com/paper/2410.07095/) (2024)
- [Improve Mathematical Reasoning in Language Models by Automated Process Supervision](https://mlsanity.com/paper/2406.06592/) (2024)

## Built on by (most cited first, 2 of 2)

- [The Collaboration Tax: How Much LLM Multi-Agent Systems Pay to Coordinate](https://mlsanity.com/paper/2608.22152/) (2026)
- [Science Done on a Machine by a Machine: AI Agents in Computational Chemistry](https://mlsanity.com/paper/2608.18508/) (2026)

## Abstract (arXiv)

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 https://github.com/Zehong-Wang/MDForge.