GPCR-BSD:在不同状态下的人类G蛋白结合受体的结合位点数据库
Fan Liu1,2, Han Zhou1,2,3, Xiaonong Li3
1University of Chinese Academy of Sciences, Beijing, 101408, China.
BMC bioinformatics
|November 4, 2024
概括
一个新的数据库,GPCR-BSD,为803个G蛋白结合受体 (GPCR) 提供127,990个预测的结合位点. 该资源通过详细介绍GPCR活跃和不活跃状态来帮助药物发现,fpocket和CavityPlus显示出强大的预测准确性.
科学领域:
- 生物化学和结构生物学.
- 药理学和药物发现
- 生物信息学和计算生物学
背景情况:
- G-蛋白结合受体 (GPCR) 是关键的膜蛋白,参与许多生物过程,是关键的药物标.
- 了解GPCR构造状态 (活性和非活性) 以及它们的结合口袋对于药物向相互作用研究至关重要.
- 对于GPCR绑定站点的全面数据库存在实际需求,以促进研究.
研究的目的:
- 开发和介绍GPCR结合点数据库 (GPCR-BSD),这是人类GPCR预测结合点的全面资源.
- 系统地评估基于几何的口袋预测方法 (fpocket,CavityPlus,GHECOM) 对GPCR的性能.
- 为查询,可视化和比较GPCR绑定网站提供一个免费可访问的平台.
主要方法:
- 利用了三种基于几何的口袋预测算法 (fpocket,CavityPlus,GHECOM) 来识别预测的GPCR结构中的结合点.
- 收集了803个GPCR的127,990个预测的结合点,遍及活跃状态和不活跃状态 (总共1,606个结构).
- 使用132个经过实验确定的人类GPCR结构评估预测准确度,评估口袋残留范围,中心距离和重复成功.
主要成果:
- GPCR-BSD数据库包含803个GPCR在活跃和不活跃状态中的预测.
- fpocket和CavityPlus方法表现出卓越的性能,在超过60%的评估实验结构中准确预测了orthosteric结合部位.
- 这项研究提供了首次对fpocket和CavityPlus用于GPCR结合部位预测的系统评估.
结论:
- GPCR-BSD数据库为研究GPCR和开发新疗法的研究人员提供了宝贵的资源.
- 这些发现证实fpocket和CavityPlus是预测GPCR结合位点的有效工具,有助于药物设计.
- 这项工作解决了对可访问和可靠的GPCR绑定站点信息的关键需求.
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