Pharmaceuticals, Volume 15, Issue 11
2022 November - 139 articles
Cover Story: G-protein-coupled receptors (GPCRs) are amongst the most pharmaceutically relevant protein targets, yet unanswered questions leave significant gaps in our understanding of their nuanced structure and function. Three-dimensional pharmacophore models are powerful computational drug discovery tools, presenting opportunities for the integration of GPCR structural biology and cheminformatics. Our review highlights successes in the application of 3D pharmacophore modeling to de novo drug design, scaffold hopping, QSAR analysis, hit-to-lead optimization, GPCR de-orphanization, the mechanistic understanding of GPCRs, and the elucidation of ligand–receptor interactions. The incorporation of dynamics and machine learning is examined. We analyze challenges facing GPCR drug discovery, detailing how 3D pharmacophore modeling can address them. View this paper - Issues are regarded as officially published after their release is announced to the table of contents alert mailing list .
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