arXiv:2604.18467cs.LGcs.AI2026-04

整合预测与生成,一键筛选高活性肽段并定向设计新肽。

An Integrated Deep-Learning Framework for Peptide-Protein Interaction Prediction and Target-Conditioned Peptide Generation with ConGA-PepPI and TC-PepGen

论文配图:An Integrated Deep-Learning Framework for Peptide-Protein Interaction Prediction and Target-Conditioned Peptide Generation with ConGA-PepPI and TC-PepGen
图 1 · 摘自论文原文
  • 用双向注意力+渐进迁移,精准预测肽蛋白结合位点。
  • 生成肽段中40.39%比天然模板更优,且保持靶点特异性。
  • 适合药物研发人员快速设计靶向肽类候选分子。

肽-蛋白相互作用(PepPI)在细胞调控和肽类治疗中至关重要,但实验表征速度慢,难以大规模筛选。现有方法多侧重于预测或生成,缺乏对候选优先级、残基级解释及靶点条件扩展的整合。我们提出一个集成框架,包含伙伴感知的预测与定位模型ConGA-PepPI和靶点条件生成模型TC-PepGen。ConGA-PepPI采用非对称编码、双向交叉注意力,并通过从配对预测到结合位点定位的渐进迁移;TC-PepGen则通过逐层条件化,在自回归解码中保留靶点信息。五折交叉验证中,ConGA-PepPI准确率达0.839,AUROC为0.921,蛋白质侧与肽段侧的结合位点AUPR分别为0.601和0.950,外部基准表现仍具竞争力。在长度受控基准下,TC-PepGen生成的40.39%肽段在AlphaFold 3 ipTM上超过天然模板,无约束生成也体现靶点条件信号。

原文摘要 · Abstract (English)

Motivation: Peptide-protein interactions (PepPIs) are central to cellular regulation and peptide therapeutics, but experimental characterization remains too slow for large-scale screening. Existing methods usually emphasize either interaction prediction or peptide generation, leaving candidate prioritization, residue-level interpretation, and target-conditioned expansion insufficiently integrated. Results: We present an integrated framework for early-stage peptide screening that combines a partner-aware prediction and localization model (ConGA-PepPI) with a target-conditioned generative model (TC-PepGen). ConGA-PepPI uses asymmetric encoding, bidirectional cross-attention, and progressive transfer from pair prediction to binding-site localization, while TC-PepGen preserves target information throughout autoregressive decoding via layerwise conditioning. In five-fold cross-validation, ConGA-PepPI achieved 0.839 accuracy and 0.921 AUROC, with binding-site AUPR values of 0.601 on the protein side and 0.950 on the peptide side, and remained competitive on external benchmarks. Under a controlled length-conditioned benchmark, 40.39% of TC-PepGen peptides exceeded native templates in AlphaFold 3 ipTM, and unconstrained generation retained evidence of target-conditioned signal.

肽设计生成模型蛋白互作AI制药

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