Multi-Agent Collaboration for Automated Design Exploration on High Performance Computing Systems

Drug discovery remains a resource-intensive and time-consuming process, involving billions of dollars and a decade of development to advance a drug to market. While many in silico tools have accelerated this process, operating them still demands substantial time, effort, and expertise from medicinal chemists. Autonomous systems built on Large Language Models (LLMs) have emerged as a promising solution, yet current designs limit their performance. Existing single-agent systems scale poorly to long-horizon, multi-step, and realistic tasks, whereas multi-agent systems typically execute predefined workflows that cannot capture the iterative, non-linear nature of a real drug discovery campaign. Here, we present MADDIE, a multi-agent drug discovery engine. It comprises a central agent, Orchestrator, and four specialized worker agents: HitIdentifier, LeadOptimizer, Synthesizer, and Evaluator, each representing a critical step in a drug discovery campaign. Under Orchestrator's orchestration and coordination, these worker agents are composed into flexible workflows, enabling MADDIE to adapt its strategy and navigate the drug discovery pipeline end-to-end. Across 50 protein targets, MADDIE produces molecules satisfying key property requirements and their synthesis routes, outperforming existing agentic systems, generative models, and general-purpose LLMs by a wide margin. Our analysis reveals how these agents collaborate and that MADDIE can employ different strategies across targets to achieve the campaign's goal, while still being efficient in time and tokens. Together, they demonstrate MADDIE as a low-cost, effective, and efficient autonomous engine for accelerating drug discovery. Code and dataset is available via https://github.com/ninglab/MADDIE.

The integration of Artificial Intelligence (AI) with High-Performance Computing (HPC) is transforming scientific workflows from human-directed pipelines into adaptive systems capable of autonomous decision-making. Large language models (LLMs) play a critical role in autonomous workflows; however, deploying LLM-based agents at scale remains a significant challenge. Single-agent architectures and sequential tool calls often become serialization bottlenecks when executing large-scale simulation campaigns, failing to utilize the massive parallelism of exascale resources. To address this, we present a scalable, hierarchical multi-agent framework for orchestrating high-throughput screening campaigns. Our planner-executor architecture employs a central planning agent to dynamically partition workloads and assign subtasks to a swarm of parallel executor agents. All executor agents interface with a shared Model Context Protocol (MCP) server that orchestrates tasks via the Parsl workflow engine. To demonstrate this framework, we employed the open-weight gpt-oss-120b model to orchestrate a high-throughput screening of the Computation-Ready Experimental (CoRE) Metal-Organic Framework (MOF) database for atmospheric water harvesting. The results demonstrate that the proposed agentic framework enables efficient and scalable execution on the Aurora supercomputer, with low orchestration overhead and high task completion rates. This work establishes a flexible paradigm for LLM-driven scientific automation on HPC systems, with broad applicability to materials discovery and beyond.

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.