Consensus 3D model of μ-opioid receptor ligand efficacy based on a quantitative Conformationally Sampled Pharmacophore.
作者： Jihyun Shim , Andrew Coop , Alexander D. MacKerell
DOI: 10.1021/JP202542G
关键词:
摘要: Despite being studied for over 30 years, a consensus structure–activity relationship (SAR) that encompasses the full range peptidic and nonpeptidic μ-opioid receptor ligands is still not available. To achieve SAR Conformationally Sampled Pharmacophore (CSP) method was applied to develop predictive model of efficacy ligands. Emphasis placed on predicting wide agonists, partial antagonists as well understanding their mode interaction with receptor. Inclusion all accessible conformations each ligand, central feature CSP method, enabled structural features between diverse dictate be identified. The models were validated against collection ligands, including benzomorphans, fentanyl (4-anilinopiperidine), methadone (3,3-diphenylpropylamines), etonitazene (benzimidazole derivatives), funaltrexamine (C6-substituted 4,5-epo...
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