ZINC-22─A Free Multi-Billion-Scale Database of Tangible Compounds for Ligand Discovery.
ZINC-22─A Free Multi-Billion-Scale Database of Tangible Compounds for Ligand Discovery.
复制标题
ZINC-22─用于配体发现的免费数十亿级有形化合物数据库。
DOI：
10.1021/acs.jcim.2c01253
复制
发表时间：
2023-02-27
影响因子：
5.6
通讯作者：
Irwin, John J.
中科院分区：
文献类型：
--
作者：
Tingle, Benjamin I.;Tang, Khanh G.;Castanon, Mar;Khurelbaatar, Munkhzul;Dandarchuluun, Chinzorig;Moroz, Yurii S.;Irwin, John J.
可购买的化学空间已迅速增长到数百亿个分子，为配体发现提供了前所未有的机会，但也给大规模利用这些分子的工具带来了压力。因此，我们开发了 ZINC-22，这是一个源自数十亿规模按需生产库的商业小分子数据库。新的数据库和工具可以通过简单的 GUI CartBlanche 在这个广阔的新空间中进行模拟搜索，利用分子数量亚线性缩放的相似性方法。新库还使用数据组织方法，能够快速查找分子及其物理特性，包括构象、部分原子电荷、cLogP 值和溶剂化能，这些对于分子对接都至关重要，而在以前版本的 ZINC 中，旧数据库组织的速度变得很慢。随着文库的不断增长，我们一直有兴趣发现分子多样性是否受到影响，例如，因为某些支架通过简单的模拟已经占据主导地位。迄今为止这种情况尚未发生，化学多样性随着数据库大小的增加而继续增长，数据库大小每增加两个对数单位，Bemis-Murcko 支架就会增加对数。大多数新支架来自重原子数最高的化合物。最后，我们考虑随着 ZINC 等数据库向万亿分子范围发展并超出万亿分子范围，这对数据库产生的影响。 ZINC 可供所有人免费使用，并且可以在 cartblanche22.docking.org、Globus 以及 Amazon AWS 和 Oracle OCI 云中访问。
Purchasable chemical space has grown rapidly into the tens of billions of molecules, providing unprecedented opportunities for ligand discovery but straining the tools that might exploit these molecules at scale. We have therefore developed ZINC-22, a database of commercially accessible small molecules derived from multi-billion-scale make-on-demand libraries. The new database and tools enable analog searching in this vast new space via a facile GUI, CartBlanche, drawing on similarity methods that scale sublinearly in the number of molecules. The new library also uses data organization methods, enabling rapid lookup of molecules and their physical properties, including conformations, partial atomic charges, c Log P values, and solvation energies, all crucial for molecule docking, which had become slow with older database organizations in previous versions of ZINC. As the libraries have continued to grow, we have been interested in finding whether molecular diversity has suffered, for instance, because certain scaffolds have come to dominate via easy analoging. This has not occurred thus far, and chemical diversity continues to grow with database size, with a log increase in Bemis–Murcko scaffolds for every two-log unit increase in database size. Most new scaffolds come from compounds with the highest heavy atom count. Finally, we consider the implications for databases like ZINC as the libraries grow toward and beyond the trillion-molecule range. ZINC is freely available to everyone and may be accessed at cartblanche22.docking.org, via Globus, and in the Amazon AWS and Oracle OCI clouds.
登录
查看更多内容
影响因子：
5.6
作者：
Grebner, Christoph;Malmerberg, Erik;Sadowski, Jens
通讯作者：
Sadowski, Jens
影响因子：
5.6
作者：
Li, Yibo;Hu, Jianxing;Liu, Zhenming
通讯作者：
Liu, Zhenming
影响因子：
5.6
作者：
Irwin JJ;Tang KG;Young J;Dandarchuluun C;Wong BR;Khurelbaatar M;Moroz YS;Mayfield J;Sayle RA
通讯作者：
Sayle RA
影响因子：
5.6
作者：
Gu S;Smith MS;Yang Y;Irwin JJ;Shoichet BK
通讯作者：
Shoichet BK
影响因子：
5.6
作者：
Irwin JJ;Sterling T;Mysinger MM;Bolstad ES;Coleman RG
通讯作者：
Coleman RG