药物领域 (DrugDomain):药物和与领域相结合的小分子的进化背景
Kirill E Medvedev1, R Dustin Schaeffer1, Nick V Grishin1,2
1Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
概括
药物域数据库将人类蛋白质域与小分子药物联系起来,通过了解蛋白质与药物相互作用,有助于发现新的药物标.
科学领域:
- 生物化学和结构生物学
- 药物发现和开发 药物发现和开发
- 生物信息学和计算生物学
背景情况:
- 小有机化合物 (药物) 与蛋白质相互作用,调节它们的功能,如酶活性和信号传递.
- 了解药物向蛋白质域相互作用是新目标发现的关键,特别是复杂蛋白质.
- 现有的蛋白质域分类缺乏综合的药物相互作用数据.
研究的目的:
- 介绍DrugDomain数据库,这是一个新的资源,将蛋白质域与药物分子联系起来.
- 为了促进对蛋白质域级别的药物向相互作用的理解.
- 通过分析进化蛋白质域分类来支持新治疗点的发现.
主要方法:
- 从蛋白质域 (ECOD) 的进化分类与DrugBank分子和药物的综合数据.
- 利用实验确定的蛋白质结构和AlphaFold模型进行域分析.
- 开发了一个数据库来报告人类蛋白质和药物分子的ECOD域之间的相互作用.
主要成果:
- 试点版的DrugDomain包括5160个与2573个人类蛋白质相关的DrugBank分子.
- 它涵盖了所有实验确定结构的领域,并在必要时包括AlphaFold模型.
- 提供了药物向蛋白质域相互作用的全面视图.
结论:
- 药物域数据库是探索药物向蛋白质域关系的宝贵资源.
- 它增强了识别新药标和理解药物机制的机会.
- 该数据库在网上公开提供,供研究使用.
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