Abstract：
: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.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Nakano H,Miyao T,Funatsu Kdoi
10.1021/acs.jcim.0c00098subject
Has Abstractpub_date
2020-04-27 00:00:00pages
2073-2081issue
4eissn
1549-9596issn
1549-960Xjournal_volume
60pub_type
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