Virtual exploration of the chemical universe up to 11 atoms of C, N, O, F: Assembly of 26.4 million structures (110.9 million stereoisomers) and analysis for new ring systems, stereochemistry, physicochemical properties, compound classes, and drug discovery
Virtual exploration of the chemical universe up to 11 atoms of C, N, O, F: Assembly of 26.4 million structures (110.9 million stereoisomers) and analysis for new ring systems, stereochemistry, physicochemical properties, compound classes, and drug discovery
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DOI：
10.1021/ci600423u
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发表时间：
2007-03-01
影响因子：
5.6
通讯作者：
Reymond, Jean-Louis
中科院分区：
文献类型：
--
作者：
Fink, Tobias;Reymond, Jean-Louis
在考虑简单化合价、化学稳定性和合成可行性规则的情况下，生成并收集所有可能的C、N、O和F的多达11个原子的分子，并将其收集在数据库（GDB）中。GDB含有2640万个分子（1.109亿个立体异构体），包括三元环和四元环以及三键。相比之下，在公共数据库（PubChem，ChemACX，ChemSCX，NCI开放数据库和默克索引的组合）中，只有63857种化合物的原子数不超过11个。GDB中的1208个环系统中，共有538个在CAS登记处和贝尔斯坦数据库中以任何碳/杂原子/多键组合或作为亚结构是目前未知的。超过70%的GDB分子是手性的。由于它们的小尺寸，所有化合物都遵守Lipinski的生物利用度规则。总共有1320万种化合物也遵循康格里夫的“3规则”。自相关描述符训练的Kohonen地图根据化合物类别组织GDB，并显示类铅化合物在稠合碳环和稠合杂环的手性区域中最丰富。已知化合物在这张地图上的投影表明了化学空间的大片未知区域。GDB用于药物发现的潜力通过激酶抑制剂、G蛋白偶联受体配体和离子通道调节剂的虚拟筛选来说明。该数据库可从作者的网页上查阅。
All molecules of up to 11 atoms of C, N, O, and F possible under consideration of simple valency, chemical stability, and synthetic feasibility rules were generated and collected in a database (GDB). GDB contains 26.4 million molecules (110.9 million stereoisomers), including three- and four-membered rings and triple bonds. By comparison, only 63 857 compounds of up to 11 atoms were found in public databases (a combination of PubChem, ChemACX, ChemSCX, NCI open database, and the Merck Index). A total of 538 of the 1208 ring systems in GDB are currently unknown in the CAS Registry and Beilstein databases in any carbon/heteroatom/multiple-bond combination or as a substructure. Over 70% of GDB molecules are chiral. Because of their small size, all compounds obey Lipinski's bioavailability rule. A total of 13.2 million compounds also follow Congreve's "Rule of 3" for lead-likeness. A Kohonen map trained with autocorrelation descriptors organizes GDB according to compound classes and shows that leadlike compounds are most abundant in chiral regions of fused carbocycles and fused heterocycles. The projection of known compounds into this map indicates large uncharted areas of chemical space. The potential of GDB for drug discovery is illustrated by virtual screening for kinase inhibitors, G-protein coupled receptor ligands, and ion-channel modulators. The database is available from the author's Web page.