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bioRxiv · 10.64898/2026.04.02.716083

PRISM: A High-Throughput Simulation Infrastructure for CADD Agents

Shi, Z.·Gao, X.·Xu, M.·Zhu, X.·Wang, P.·Yang, Y.·Yang, Z.·Zhou, R.
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Abstract

Despite rapid progress in AI agents for computer-aided drug design (CADD), protein-ligand simulation workflows remain fragmented across disparate tools, creating a major bottleneck for scalable candidate evaluation. Here, we present PRISM (Protein-Receptor Interaction Simulation Modeler), a Python platform built on GROMACS that unifies ligand parameterization across multiple force fields, automated system construction, enhanced sampling, multi-tier binding free energy estimation, and trajectory analysis within a single workflow. Through the Model Context Protocol (MCP), PRISM further serves as the computational infrastructure for CADD-Agent, an expert-workflow-driven AI agent designed to orchestrate hierarchical drug screening pipelines. As a pilot application, we applied PRISM to riboflavin synthase and demonstrated end-to-end automation from candidate library assembly to binding pocket characterization, identifying a potential allosteric inhibition site at the oligomerization interface. Together, these results establish PRISM as a high-throughput simulation infrastructure for agent-enabled CADD.

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Shi, Z., Gao, X., Xu, M., Zhu, X., Wang, P., Yang, Y., Yang, Z., Zhou, R.. 2026-04-06. PRISM: A High-Throughput Simulation Infrastructure for CADD Agents. https://doi.org/10.64898/2026.04.02.716083

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