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Drug Repurposing on G Protein-Coupled Receptors Using a Computational Profiling Approach
- Source :
- Frontiers in Molecular Biosciences, Vol 8 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- G protein-coupled receptors (GPCRs) are the largest human membrane receptor family regulating a wide range of cell signaling. For this reason, GPCRs are highly desirable drug targets, with approximately 40% of prescribed medicines targeting a member of this receptor family. The structural homology of GPCRs and the broad spectrum of applications of GPCR-acting drugs suggest an investigation of the cross-activity of a drug toward different GPCR receptors with the aim of rationalizing drug side effects, designing more selective and less toxic compounds, and possibly proposing off-label therapeutic applications. Herein, we present an original in silico approach named “Computational Profiling for GPCRs” (CPG), which is able to represent, in a one-dimensional (1D) string, the physico-chemical properties of a ligand–GPCR binding interaction and, through a tailored alignment algorithm, repurpose the ligand for a different GPCR. We show three case studies where docking calculations and pharmacological data confirm the drug repurposing findings obtained through CPG on 5-hydroxytryptamine receptor 2B, beta-2 adrenergic receptor, and M2 muscarinic acetylcholine receptor. The CPG code is released as a user-friendly graphical user interface with numerous options that make CPG a powerful tool to assist the drug design of GPCR ligands.
Details
- Language :
- English
- ISSN :
- 2296889X
- Volume :
- 8
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Molecular Biosciences
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.7c232f6c84174c0fb1230ed20cc93b56
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fmolb.2021.673053