混合双语境促成交叉注意力框架与语言模型指导,用于多标签预测人类非目标干-蛋白相互作用
Abdullah1,2, Zulaikha Fatima3, Muhammad Ateeb Ather1,2
1Center for Computing Research, Instituto Politécnico Nacional, Mexico City 07320, Mexico.
International journal of molecular sciences
|January 28, 2026
概括
本研究介绍了HDPC-LGT,这是一个深度学习框架,用于预测药物异常目标和降低毒性. 它准确地识别了联体蛋白相互作用,改善了药物发现和安全概况.
科学领域:
- 计算化学和药物发现
- 生物信息学和计算生物学
- 制药研究中的人工智能
背景情况:
- 准确的药物脱标识对于药物开发至关重要,但当前的深度学习方法难以整合各种数据类型.
- 预测连接体与蛋白质的结合对于降低药物毒性和提高药物发现成功率至关重要.
- 现有的模型往往无法有效地融合化学结构,蛋白质生物学和多目标信息.
研究的目的:
- 引入HDPC-LGT (混合双引发交叉注意力联体-蛋白质图形转换器),这是一个用于预测联体与蛋白质结合的新框架.
- 开发一种能够整合化学结构,蛋白质语言模型嵌入和结构先验的模型,以进行可靠的相互作用预测.
- 预测与抗生素毒性相关的16种人类翻译相关蛋白质的连接键结合.
主要方法:
- HDPC-LGT将基于图形的化学表示与蛋白质语言模型嵌入和结构信息相结合.
- 该框架使用来自ChEMBL和BindingDB.DB的超过216,000个经过实验验证的配体蛋白对进行了训练.
- 模型性能使用严格的脚手架级,蛋白质级和联合持久策略进行评估,并与Papyrus,PDBbind和Yamanishi等外部数据集一起进行评估.
主要成果:
- HDPC-LGT实现了0.996的宏观ROC-AUC和0.989的微型F1得分,明显超过现有的最先进模型 (DeepDTA,GraphDTA,MolTrans,CAT-DTI,HGT-DTA) 的3-7%.
- 外部验证数据集证实了该模型对新化学结构和蛋白质的强大概括能力.
- 可解释性方法 (交叉注意力图,IG,Grad-CAM) 突出了关键相互作用和残留物,与已知的生化机制保持一致.
结论:
- HDPC-LGT有效地整合了多模式生物化学数据,以准确预测配体-蛋白相互作用和评估目标外毒性.
- 该框架提供了生物可解释的见解,有助于基于结构的药物设计和优化.
- HDPC-LGT为抗生素开发,安全分析和多药理学研究提供了宝贵的工具.
关键词:
相互注意的注意力交叉.深度学习是一种深度学习.发现药物的发现.图形变压器 图形变压器模型的解释性可解释性多式联络方式的代表性.在目标之外的预测预测多种药理学 多种药理学蛋白联体相互作用脚手架的一般化概括更多相关视频
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