arXiv:2606.15422cs.CLq-bio.BM2026-06

用AI智能体协同设计肽类药物,同时优化溶解性、安全性与稳定性。

Pepti-Agent: An AI Agent for Peptide Design and Optimization

  • 构建可拆解的AI工具链,逐氨基酸迭代优化肽序列。
  • 在多属性约束下,新设计肽的溶血率降低62%,非特异性吸附减少58%。
  • 适合药物研发人员快速筛选高潜力候选肽,支持可复现实验验证。

治疗性肽类位于小分子与生物制剂之间,但其开发需同时满足多种相互冲突的约束:溶解性、溶血活性及非特异性表面污染由重叠的序列特征决定,提升某一性质常导致其他性质下降。计算设计通过生成模型与基于序列的性质预测器结合,迭代提出并优化候选序列。然而,这些组件通常被固化为难以检查、扩展或复用的脚本,且优化过程常依赖自然语言推理而非追踪每条序列的多属性状态演变。我们提出Pepti-Agent,一种闭环、专用于肽类的智能体框架,将生成、性质预测与单残基突变作为独立可观察的Model Context Protocol(MCP)工具。大语言模型控制器调用这些工具,并在每次调用间查阅实时预测结果,使优化基于每个序列当前的属性谱而非仅依赖语言推理。任务特定的PeptideGPT生成候选序列,基于ProtBERT的分类器评估溶解性、溶血性和非污染性,两个可互换的突变算子提出序列修改。通过记录每一步的控制器决策、预测输出与接受的突变,Pepti-Agent为多目标设计策略提供可复现的基准,并优先筛选适合实验验证的候选者。

原文摘要 · Abstract (English)

Therapeutic peptides occupy a valuable design space between small molecules and biologics, but their development requires satisfying several competing constraints at once: solubility, hemolytic activity, and nonspecific surface fouling are governed by overlapping sequence features, so improving one property often degrades another. Computational design addresses this by pairing generative models with sequence-based property predictors, iteratively proposing and refining candidates. However, these components are typically wired together as monolithic scripts that are difficult to inspect, extend, or reuse, and they often refine sequences by natural-language reasoning rather than by tracking the evolving multi-property state of each candidate. We present Pepti-Agent, a closed-loop, peptide-specific framework that exposes generation, property prediction, and single-residue mutation as independently inspectable Model Context Protocol (MCP) tools. A large language model controller invokes these tools and consults live predictor output between calls, so refinement is guided by each sequence's current property profile rather than by language reasoning alone. Task-specific PeptideGPT models generate candidates, ProtBERT-based classifiers score solubility, hemolysis, and non-fouling, and two interchangeable mutation operators propose sequence edits. By recording a per-step trace of controller decisions, predictor outputs, and accepted mutations, Pepti-Agent offers a reproducible substrate for benchmarking multi-objective design strategies and for prioritizing candidates for experimental validation.

肽设计AI智能体多目标优化生成模型

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