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Structural bioinformatics analysis of single nucleotide polymorphisms mapped to cannabinoid receptor 1

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posted on 28.03.2022, 21:37 by Syed Haneef
G protein-coupled receptors (GPCRs) are key cell membrane-embedded receptor proteins, with critical roles in cellular signal transduction. In the era of precision medicine, understanding the role of variants on GPCR function is critical, especially from a pharmacogenomics view point. A computational method has been used to map deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) to a GPCR in the endocannabinoid system, the human cannabinoid receptor 1 (CB1). Due to its central role in the endocannabinoid system, especially in the central nervous system, CB1 is an important drug target and its variability has implications for disease susceptibility and altered drug response. CB1 mutations were collated from relevant SNP databases and then computationally evaluated from neutral to deleterious. Mapping the variants on the CB1 structure showed the top twelve deleterious mutations were found to be either close to the ligand binding region or the G-protein binding site. From the top mutations, nine variants have clinical relevance, corresponding to phenotypic variations. Additionally, molecular docking analysis with a set of common ligands, variant structural analysis and, investigation of SNPs by molecular dynamics simulation, helped to understand the structural basis of `variant pathogenicity.


Table of Contents

1. Introduction -- 2. Methods -- 3. Results -- 4.Discussion -- 5. Conclusions -- References -- Supplementary material.


Bibliography: pages 37-48 Empirical thesis.

Awarding Institution

Macquarie University

Degree Type

Thesis MRes


MRes, Macquarie University, Faculty of Science and Engineering, Department of Molecular Sciences

Department, Centre or School

Department of Molecular Sciences

Year of Award


Principal Supervisor

Shoba Ranganathan

Additional Supervisor 1

Mark Connor


Copyright Syed Haneef 2019. Copyright disclaimer: http://mq.edu.au/library/copyright




1 online resource (x, 48, vii pages) diagrams, graphs, tables

Former Identifiers

mq:71091 http://hdl.handle.net/1959.14/1270757