人类 DCDC2 基因有害 SNPs 及其对后续蛋白质-蛋白质相互作用影响的硅学分析

Nure Asma Lata, N. Parvez, Sumaiya Farah Khan
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摘要

DCDC2 是一种具有临床意义的蛋白质,可导致多种神经系统疾病,因此是一种需要分析的重要蛋白质。在这项研究中,我们使用了多种工具来鉴定对该蛋白本身有害并破坏该蛋白与管蛋白亚基相互作用稳定性的错义 SNP。在分析了从 dbSNP 数据库中检索到的所有 378 个错义 SNPs 后,发现其中 13 个对该蛋白有害,它们是 L20P、R23L、G25W、G25R、D26E、I36N、G60E、P68S、G83R、T174I、L179R、R186G、V208E。其中,T174I、L179R、R186G 和 V208E 这四个 SNPs 对 C-DC 结构域与微管的相互作用具有显著的不稳定性;L20P、D26E 和 G83R 这三个 SNPs 对 N-DC 结构域与微管的相互作用具有显著的不稳定性。根据总ΔΔG值,SNP R186G和L20P似乎对C-DC和N-DC结构域的相互作用最不稳定。通过使用多种计算工具进行分析,发现这些 SNP 对蛋白质有负面影响。以这些 SNPs 为重点的遗传关联和蛋白质相互作用研究可以揭示有关阅读障碍或其他神经发育障碍的新发现。J. Bangladesh Acad.47(2); 181-193:2023 年 12 月
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In silico analysis of deleterious SNPs of human DCDC2 gene and their impacts on subsequent protein-protein interactions
DCDC2 is a clinically significant protein causing a number of neurological disorders and, hence, is an important protein for analysis. In this study, multiple tools were employed to identify missense SNPs that are harmful to the protein itself and destabilize the interaction of this protein with tubulin subunits. After analyzing all 378 missense SNPs retrieved from the dbSNP database, thirteen were found to have harmful effects on the protein, which are L20P, R23L, G25W, G25R, D26E, I36N, G60E, P68S, G83R, T174I, L179R, R186G, V208E. Among these, four SNPs- T174I, L179R, R186G, and V208E were suggested to be significantly destabilizing for the interaction of the C-DC domain with microtubule, and three SNPs- L20P, D26E, and G83R for the interaction of N-DC domain with microtubule. Based on the total ΔΔG value, SNP R186G and L20P seem most destabilizing for the interaction of the C-DC and N-DC domains. These SNPs are found to affect the protein negatively by analysis using several computational tools. Genetic association and protein-protein interaction studies focused on these SNPs can reveal new findings about dyslexia or other neurodevelopmental disorders. J. Bangladesh Acad. Sci. 47(2); 181-193: December 2023
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