Johnson & Johnson Pharmaceutical Research & Development, LLC, Welsh & McKean Roads, Spring House, Pennsylvania 19477, USA.
J Med Chem. 2010 Jul 8;53(13):5002-11. doi: 10.1021/jm1004495.
We introduce Scaffold Explorer, an interactive tool that allows medicinal chemists to define hierarchies of chemical scaffolds and use them to explore their project data. Scaffold Explorer allows the user to construct a tree, where each node corresponds to a specific scaffold. Each node can have multiple children, each of which represents a more refined substructure relative to its parent node. Once the tree is defined, it can be mapped onto any collection of compounds and be used as a navigational tool to explore structure-activity relationships (SAR) across different chemotypes. The rich visual analytics of Scaffold Explorer afford the user a "bird's-eye" view of the chemical space spanned by a particular data set, map any physicochemical property or biological activity of interest onto the individual scaffold nodes, serve as an aggregator for the properties of the compounds represented by these nodes, and quickly distinguish promising chemotypes from less interesting or problematic ones. Unlike previous approaches, which focused on automated extraction and classification of scaffolds, the utility of the new tool rests on its interactivity and ability to accommodate the medicinal chemists' intuition by allowing the use of arbitrary substructures containing variable atoms, bonds, and/or substituents such as those employed in substructure search.
我们介绍了 Scaffold Explorer，这是一个交互式工具，允许药物化学家定义化学支架的层次结构，并使用它们来探索他们的项目数据。Scaffold Explorer 允许用户构建一棵树，其中每个节点对应于特定的支架。每个节点可以有多个子节点，每个子节点相对于其父节点表示更精细的子结构。一旦定义了树，就可以将其映射到任何化合物集合上，并用作导航工具，以探索不同化学类型的结构-活性关系 (SAR)。Scaffold Explorer 的丰富可视化分析为用户提供了特定数据集所涵盖的化学空间的“鸟瞰图”，可以将任何感兴趣的物理化学性质或生物活性映射到单个支架节点上，作为这些节点所代表的化合物性质的聚合器，并快速区分有前途的化学类型和不太有趣或有问题的化学类型。与以前专注于自动提取和分类支架的方法不同，新工具的实用性在于其交互性和通过允许使用包含可变原子、键和/或取代基的任意子结构（如在子结构搜索中使用的那些）来适应药物化学家的直觉的能力。
