Toward a Universal μ-Agonist Template for Template-Based Alignment Modeling of Opioid Ligands

Zhijun Wu, Victor J. Hruby

Research output: Contribution to journalArticle

Abstract

Opioid ligands are a large group of G-protein-coupled receptor ligands possessing high structural diversity, along with complicated structure-activity relationships (SARs). To better understand their structural correlations as well as the related SARs, we developed the innovative template-based alignment modeling in our recent studies on a variety of opioid ligands. As previously reported, this approach showed promise but also with limitations, which was mainly attributed to the small size of morphine as a template. With this study, we set out to construct an artificial μ-agonist template to overcome this limitation. The newly constructed template contained a largely extended scaffold, along with a few special μ-features relevant to the μ-selectivity of opioid ligands. As demonstrated in this paper, the new template showed significantly improved efficacy in facilitating the alignment modeling of a wide variety of opioid ligands. This report comprises of two main parts. Part 1 discusses the general construction process and the structural features as well as a few typical examples of the template applications and Part 2 focuses on the template refinement and validation.

Original languageEnglish (US)
Pages (from-to)17457-17476
Number of pages20
JournalACS Omega
Volume4
Issue number17
DOIs
Publication statusPublished - Oct 22 2019

    Fingerprint

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this