Diameter is a key 3D characteristic for assessments of efficient inhibitors of protein-protein interactions

Masakazu Nakadai, Shuta Tomida

Research output: Contribution to journalArticlepeer-review

Abstract

Three-dimensional (3D) molecular descriptors, including physicochemical and shape properties, for protein-protein interaction (PPI) interface inhibitors have become a topic of discussion. However, the relationships between such properties and binding free energy have not been adequately investigated. In this study, we focused on identifying key 3D molecular descriptors related to the binding free energy and/or the ligand efficiency (LE) of PPI interface inhibitors. A positive correlation was found between the binding free energy and the diameter (D) of cylindrical 3D molecules, in addition to a correlation between LE and D/heavy atom count (HAC). In addition, we showed a correlation between LE and D/HAC for macrocyclic compounds, suggesting that the present findings could be applied during assessments of the potential of macrocyclic PPI interface inhibitors in drug discovery processes.

Original languageEnglish
Pages (from-to)4785-4790
Number of pages6
JournalJournal of Chemical Information and Modeling
Volume60
Issue number10
DOIs
Publication statusPublished - Oct 26 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences

Fingerprint Dive into the research topics of 'Diameter is a key 3D characteristic for assessments of efficient inhibitors of protein-protein interactions'. Together they form a unique fingerprint.

Cite this