当前位置: X-MOL 学术J. Chem. Inf. Model. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Exploring Topological Pharmacophore Graphs for Scaffold Hopping.
Journal of Chemical Information and Modeling ( IF 5.6 ) Pub Date : 2020-03-23 , DOI: 10.1021/acs.jcim.0c00098
Hiroshi Nakano 1 , Tomoyuki Miyao 1, 2 , Kimito Funatsu 1, 2, 3
Affiliation  

The primary goal of ligand-based virtual screening is to identify active compounds consisting of a core scaffold that is not found in the current active compound pool. Scaffold hopping is the term used for this purpose. In the present study, topological representations of pharmacophore features on chemical graphs were investigated for scaffold hopping. Pharmacophore graphs (PhGs), which consist of pharmacophore features as nodes and their topological distances as edges, were used as a representation of important information on compounds being active. We investigated ranking methods for prioritizing PhGs for scaffold hopping. The proposed method, NScaffold, which ranks PhGs based on the number of scaffolds covered by the PhGs, outperforms other conventional methods. As a demonstrative case, using a thrombin inhibitor data set, we interpreted the highest-ranked PhGs by NScaffold from the protein-ligand interaction point of view. It resulted that the NScaffold method successfully retrieved three known important interactions, showing the potential for identifying scaffold-hopped compounds with interpretable PhGs.

中文翻译:

探索用于支架跳跃的拓扑药理图。

基于配体的虚拟筛选的主要目标是鉴定由当前活性化合物库中未发现的核心骨架组成的活性化合物。支架跳跃是用于此目的的术语。在本研究中,研究了药效学特征在拓扑图上的拓扑表示,以研究支架跳跃。药典图(PhGs)由药效团特征作为结点,其拓扑距离作为边缘,被用来表示有关活性化合物的重要信息。我们调查了优先考虑支架跳动的PhG的排名方法。所提出的方法NScaffold基于PhG覆盖的支架数量对PhG进行排名,其性能优于其他常规方法。作为示例,使用凝血酶抑制剂数据集,我们从蛋白质-配体相互作用的角度解释了NScaffold排名最高的PhG。结果表明,NScaffold方法成功检索了三个已知的重要相互作用,显示了用可解释的PhGs鉴定脚手架跳跃化合物的潜力。
更新日期:2020-03-23
down
wechat
bug