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Method for Systematic Assessment of Chemical Changes in Molecular Scaffolds with Conserved Topology and Application to the Analysis of Scaffold‐Activity Relationships
Author(s) -
Hu Ye,
Zhang Bijun,
Bajorath Jürgen
Publication year - 2015
Publication title -
molecular informatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.481
H-Index - 68
eISSN - 1868-1751
pISSN - 1868-1743
DOI - 10.1002/minf.201500034
Subject(s) - topology (electrical circuits) , scaffold , heteroatom , chemistry , computer science , mathematics , organic chemistry , ring (chemistry) , combinatorics , database
Abstract Sets of scaffolds with conserved molecular topology are abundant among drugs and bioactive compounds. Core structure topology is one of the determinants of biological activity. Heteroatom replacements and/or bond order variation render topologically equivalent scaffolds chemically distinct and also contribute to differences in the biological activity of compounds containing these scaffolds. Relationships between core structure topology, chemical modifications, and observed activity profiles are difficult to analyze. A computational method is introduced to consistently assess chemical transformations that distinguish scaffolds with conserved topology. The methodology is applied to quantify chemical differences in conserved topological environments and systematically relate chemical changes in topologically equivalent scaffolds to associated activity profiles.