药物领域2.0:在整个蛋白质数据库中对蛋白质域-配体/药物相互作用的全面数据库
Kirill E Medvedev1,2, R Dustin Schaeffer1, Nick V Grishin1,3
1Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
DrugDomain v2.0是一个新的数据库,将蛋白质进化域 (ECOD) 与配体相互作用联系起来,使用结构数据和AI预测来映射药物标和蛋白质功能.
科学领域:
- 结构生物学是结构生物学.
- 生物信息学是一种生物信息学.
- 计算生物学是一种计算生物学.
背景情况:
- 蛋白质通过与其结构域内的小分子和药物相互作用来执行重要的细胞功能.
- 蛋白质域是推动进化的保存单位,蛋白质域的进化分类 (ECOD) 层次揭示了远程的进化关系.
- 在结构层面上系统地绘制蛋白质域-连接体相互作用时存在差距.
研究的目的:
- 介绍DrugDomain v2.0,这是第一个全面的数据库,将ECOD分类与连接因子结合事件联系起来.
- 用人工智能预测扩展域-联体注释到缺乏实验结构的人类药物标,使用人工智能预测.
- 为了解蛋白质 - 配体相互作用和药物发现提供一个有价值的资源.
主要方法:
- 来自蛋白质数据库 (PDB) 和DrugBank的综合数据.
- 利用AlphaFold的AI驱动预测进行结构建模.
- 开发了一个数据库,将ECOD分类与实验确定和预测的域-连接物相互作用联系起来.
主要成果:
- DrugDomain v2.0对超过37,000个PDB配体和7,560个DrugBank分子的相互作用进行了目录.
- 数据库包括6000多个小分子相关的翻译后修改 (PTM).
- 附注 14,000+ PTM 修改的人类蛋白质模型与对接联体,涵盖 43,023 UniProt 加入和 174,545 PDB 结构.
结论:
- DrugDomain v2.0 弥合了结构域-连接物相互作用数据的差距.
- 该数据库增强了对蛋白质功能,进化和药物相互作用的理解.
- 为人工智能驱动的药物发现和个性化医学提供基础.
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