Visual Characterization and Diversity Quantification of Chemical Libraries: 1. Creation of Delimited Reference Chemical Subspaces
Visual Characterization and Diversity Quantification of Chemical Libraries: 1. Creation of Delimited Reference Chemical Subspaces
复制标题
DOI：
10.1021/ci200051r
复制
发表时间：
2011-08-01
影响因子：
5.6
通讯作者：
Morin-Allory, Luc
中科院分区：
文献类型：
--
作者：
Le Guilloux, Vincent;Colliandre, Lionel;Morin-Allory, Luc
高通量筛选（HTS）是一项成熟的技术，可以在几周内测试多达数百万种化合物。尽管有这些吸引人的能力，但可用的资源和高成本可能会限制筛选的分子数量，使多样性分析成为设计和优先筛选文库的首选方法。随着可用于筛选的分子数量的不断增加，化学空间已成为可视化，分析和比较化学库的关键概念。在这第一篇文章中，我们提出了一种新的方法来建立定界参考化学子空间（DRCS）。从73家化学品供应商收集了1600万种筛选化合物，形成了一个包含663万个标准化和独特分子的数据库。这些分子已被用来创建三个DRCS使用三个不同的化学描述符集。已经获得了每个空间的鲁棒的主成分分析模型，从而将分子投影在减小的二维可视空间中。我们的方法的特殊性在于，每个减少的空间已经由一个代表性的轮廓界定，该轮廓包含非常大比例的分子并反映其整体形状。通过映射和比较各种化学库来说明该方法。在这些研究中使用的几个工具是免费提供的，从而使任何用户计算DRCS匹配的具体要求。
High-throughput screening (HTS) is a well-established technology which can test up to several million compounds in a few weeks. Despite these appealing capabilities, available resources and high costs may limit the number of molecules screened, making diversity analysis a method of choice to design and prioritize screening libraries. With a constantly increasing number of molecules available for screening, chemical space has become a key concept for visualizing, analyzing, and comparing chemical libraries. In this first article, we present a new method to build delimited reference chemical subspaces (DRCS). A set of 16 million screening compounds from 73 chemical providers has been gathered, resulting in a database of 6.63 million standardized and unique molecules. These molecules have been used to create three DRCS using three different sets of chemical descriptors. A robust principal component analysis model for each space has been obtained, whereby molecules are projected in a reduced two-dimensional viewable space. The specificity of our approach is that each reduced space has been delimited by a representative contour encompassing a very large proportion of molecules and reflecting its overall shape. The methodology is illustrated by mapping and comparing various chemical libraries. Several tools used in these studies are made freely available, thus enabling any user to compute DRCS matching specific requirements.