Structure–Function Studies on Non-synonymous SNPs of Chemokine Receptor Gene Implicated in Cardiovascular Disease: A Computational Approach

• Published in: Protein Journal Vol. 32; no. 8; pp. 657 - 665
• Main Authors: Sai Ramesh, A., Sethumadhavan, Rao, Thiagarajan, Padma
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2013; Springer; Springer Nature B.V
• Subjects: Analysis; Animal Anatomy; Biochemistry; Bioorganic Chemistry; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - genetics; Chemistry; Chemistry and Materials Science; Chemokines; Chromosomes; DNA Mutational Analysis; Gene mutations; Heart attack; Histology; Humans; Molecular dynamics; Molecular Dynamics Simulation; Morphology; Mutation; Myocardial infarction; Organic Chemistry; Point Mutation; Polymorphism; Polymorphism, Single Nucleotide; Receptors, CCR5 - chemistry; Receptors, CCR5 - genetics; Single nucleotide polymorphisms; SNPs; Cardiovascular disease; Bioinformatics; Chemokine receptor 5
• ISSN: 1572-3887; 1573-4943; 1875-8355
• DOI: 10.1007/s10930-013-9529-7

Among non-communicable diseases, cardiovascular disease (CVD) is claimed to be the leading cause of death worldwide. The chemokine (C–C Motif) receptor 5 (CCR5) gene has a strong association with the development of CVD and may culminate in myocardial infarction. In this study, its potential variations have been determined using molecular dynamics approach. Single nucleotide polymorphisms (SNPs) are the predominant mutations and their deleterious effects were initially screened using prediction tools. Further, for the 75 % of deleterious non-synonymous SNPs predicted in common by the above tools, root mean square deviation (RMSD) and stability residues were determined using SWISS-PDB viewer and SRide server respectively. Accordingly, four point mutations L55Q, V131F, R223W, and G301R which had RMSD ≥2.0 Å were selected and trajectory analyses were performed. In common, all trajectory analyses reported no similarities between native and mutants. Combined mutational analysis comparing all the mutants together with the native also showed significant and similar changes. Thus we conclude that the above four mutations are the potential targets of CCR5 and may lead to CVD.