Deciphering a Pharmacophore Network: A Case Study Using BCR-ABL Data

J Chem Inf Model. 2022 Feb 14;62(3):678-691. doi: 10.1021/acs.jcim.1c00427. Epub 2022 Jan 26.

Abstract

This paper introduces a general method that can be used to create groups of pharmacophores to support their further in-depth analysis. A BCR-ABL molecular dataset was used to calculate graph edit distances between pharmacophores and led to their organization into a novel pharmacophore network. The application of a graph layout algorithm allowed us to discriminate between the pharmacophores associated with active compounds and those associated with inactive compounds. A clustering approach was used to refine the partitioning by grouping the pharmacophores based on their structures, activities, and binding modes. Analysis of a newly spatialized pharmacophore network provided us with critical insight into structure-activity relationships, most notably those that revealed distinctions between activity classes and chemical families. As shown, this method permits us to identify families of structurally homogeneous pharmacophores.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Cluster Analysis
  • Structure-Activity Relationship