School of Biosciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India.
Protein J. 2013 Dec;32(8):657-65. 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.
在非传染性疾病中，心血管疾病（CVD）被认为是全球范围内的主要死亡原因。趋化因子（C-C 基序）受体 5（CCR5）基因与 CVD 的发展密切相关，可能导致心肌梗死。在这项研究中，使用分子动力学方法确定了其潜在的变异。单核苷酸多态性（SNP）是主要的突变，最初使用预测工具筛选其有害影响。此外，对于上述工具共同预测的 75%有害非同义 SNP，使用 SWISS-PDB viewer 和 SRide 服务器分别确定均方根偏差（RMSD）和稳定残基。因此，选择了四个 RMSD≥2.0Å的点突变 L55Q、V131F、R223W 和 G301R，并进行了轨迹分析。通常，所有轨迹分析都没有报告天然和突变体之间的相似性。将所有突变体与天然体进行联合突变分析也显示出显著且相似的变化。因此，我们得出结论，上述四个突变是 CCR5 的潜在靶点，可能导致 CVD。
