RCSB Protein Data Bank: Enabling biomedical research and drug discovery
RCSB Protein Data Bank: Enabling biomedical research and drug discovery
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DOI：
10.1002/pro.3730
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发表时间：
2019-11-29
期刊：
影响因子：
8
通讯作者：
Burley, Stephen K.
中科院分区：
文献类型：
--
作者：
Goodsell, David S.;Zardecki, Christine;Burley, Stephen K.
对公开结构数据的分析揭示了对蛋白质靶点三维 (3D) 结构影响的有趣见解，这对新药的发现很重要（例如，G 蛋白偶联受体、电压门控离子通道、配体门控离子通道、转运蛋白和 E3 泛素连接酶）。蛋白质数据库 (PDB) 档案目前拥有超过 155,000 个通过晶体学、核磁共振波谱和电子显微镜实验确定的生物分子原子级 3D 结构。 PDB 成立于 1971 年，是生物学领域第一个开放获取的数字数据资源，现在由全球 PDB 合作伙伴关系 (wwPDB; ) 管理。美国 PDB 的运营由结构生物信息学 PDB 研究合作实验室 (RCSB PDB) 负责。 RCSB PDB 通过提供与类似 40 个外部生物数据资源集成的 PDB 数据，为全球数百万用户提供服务，提供基础生物学、生物医学和能源科学的丰富结构视图。最近发表的研究表明，PDB 档案馆藏促进了美国食品和药物管理局 2010-2016 年批准的 210 种新药中 90% 的类似药物的发现。我们回顾了 RCSB PDB 服务的用户驱动开发，检查了 PDB 档案在大小和复杂性方面的增长，并针对具有挑战性的目标（例如，整合膜蛋白）提供了结构引导药物发现的示例和机会。
Analyses of publicly available structural data reveal interesting insights into the impact of the three-dimensional (3D) structures of protein targets important for discovery of new drugs (e.g., G-protein-coupled receptors, voltage-gated ion channels, ligand-gated ion channels, transporters, and E3 ubiquitin ligases). The Protein Data Bank (PDB) archive currently holds > 155,000 atomic-level 3D structures of biomolecules experimentally determined using crystallography, nuclear magnetic resonance spectroscopy, and electron microscopy. The PDB was established in 1971 as the first open-access, digital-data resource in biology, and is now managed by the Worldwide PDB partnership (wwPDB; ). US PDB operations are the responsibility of the Research Collaboratory for Structural Bioinformatics PDB (RCSB PDB). The RCSB PDB serves millions of users worldwide by delivering PDB data integrated with similar to 40 external biodata resources, providing rich structural views of fundamental biology, biomedicine, and energy sciences. Recently published work showed that the PDB archival holdings facilitated discovery of similar to 90% of the 210 new drugs approved by the US Food and Drug Administration 2010-2016. We review user-driven development of RCSB PDB services, examine growth of the PDB archive in terms of size and complexity, and present examples and opportunities for structure-guided drug discovery for challenging targets (e.g., integral membrane proteins).