EnzySeek: Efficient Exploration of Enzyme Reaction Pathways Using AI Agents

Abstract

With the rapid development of Large Language Models (LLMs) and Agent technologies, AI can assist in solving a variety of real-world problems across multiple domains, such as autonomous driving, drug discovery, and materials design. In this work, we present EnzySeek, an enzyme catalysis AI agent designed to assist researchers in enzyme catalysis simulations. First, we constructed a domain-specific knowledge base by curating thousands of papers related to enzyme catalysis. Second, we customized Model Context Protocol (MCP) interfaces for each step of the enzyme catalysis simulation workflow, enabling these functions to be invoked by LLMs. Finally, we configured an agent capable of simultaneously referencing past empirical studies on enzyme catalysis, autonomously executing tool calls, and analyzing as well as presenting the results. EnzySeeks capabilities cover multiple aspects, including protein structure prediction, molecular docking, system preparation and parameterization, molecular dynamics (MD) simulations, and QM/MM calculations. The conclusions drawn by EnzySeek are primarily based on the results of QM/MM calculations. We employed the semi-empirical quantum mechanical method GFN2-xTB to calculate the QM region of the system. Benchmark results indicate that the GFN2-xTB method can achieve high efficiency while maintaining accuracy. The EnzySeek agent is designed to continuously learn from newly published literature and past computational tasks. During its operation, every AI decision is manually verified and scored by human experts. This human-in-the-loop validation provides the AI with sufficient case-based support, ultimately contributing to the full automation of enzyme catalysis computations. All data generated during the simulations are compiled into a dataset, which is used to establish evaluation criteria specific to enzyme catalysis computational results.