Computational analysis of deleterious single nucleotide polymorphisms in catechol O-Methyltransferase conferring risk to post-traumatic stress disorder.
Computational analysis of deleterious single nucleotide polymorphisms in catechol O-Methyltransferase conferring risk to post-traumatic stress disorder.
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儿茶酚O-甲基转移酶中有害单核苷酸多态性与创伤后应激障碍风险的计算分析
DOI：
10.1016/j.jpsychires.2021.03.048
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发表时间：
2021-06
影响因子：
4.8
通讯作者：
Nagarkatti M
中科院分区：
文献类型：
--
作者：
Chitrala KN;Nagarkatti P;Nagarkatti M
创伤后应激障碍(PTSD)是一种常见的神经系统疾病，在过去的几十年里引起了越来越多的关注。创伤后应激障碍的主要危险因素可分为环境因素和遗传因素。在众多的遗传危险因素中，儿茶酚氧位甲基转移酶(COMT)基因的多态与创伤后应激障碍的风险有关。在本研究中，我们使用基于计算的方法和分子动力学模拟，分析了COMT基因中有害的单核苷酸多态(SNPs)对PTSD风险的影响。有关COMT基因与创伤后应激障碍相关的数据来自多个数据库，包括在线孟德尔人遗传检索(OMIM)。从数据库SNP数据库下载了与SNP相关的数据集。为了研究COMT野生型和突变型的结构和动力学效应，我们在300 ns的时间尺度上进行了分子动力学模拟(MD模拟)。计算工具SIFT和Polyphen-2筛查SNP的结果表明，COMT中的SNP rs4680(V158M)对PTSD的表型有有害影响。分子动力学模拟结果表明，野生型和突变型COMT蛋白的结构特征包括均方根偏差、旋转半径、均方根波动和二级结构元素包括α-螺旋、片层和转角都有较大的波动。总之，我们的研究为V158M突变对COMT蛋白结构的有害影响和影响提供了新的见解，COMT蛋白结构在PTSD中起着关键作用。
Post-traumatic stress disorder (PTSD) is one of the prevalent neurological disorder which is drawing increased attention over the past few decades. Major risk factors for PTSD can be categorized into environmental and genetic factors. Among the genetic risk factors, polymorphisms in the catechol-O-methyltransferase (COMT) gene is known to be associated with the risk for PTSD. In the present study, we analysed the impact of deleterious single nucleotide polymorphisms (SNPs) in the COMT gene conferring risk to PTSD using computational based approaches followed by molecular dynamic simulations. The data on COMT gene associated with PTSD were collected from several databases including Online Mendelian Inheritance in Man (OMIM) search. Datasets related to SNP were downloaded from the dbSNP database. To study the structural and dynamic effects of COMT wild type and mutant forms, we performed molecular dynamics simulations (MD simulations) at a time scale of 300 ns. Results from screening the SNPs using the computational tools SIFT and Polyphen-2 demonstrated that the SNP rs4680 (V158M) in COMT has a deleterious effect with phenotype in PTSD. Results from the MD simulations showed that there is some major fluctuations in the structural features including root mean square deviation (RMSD), radius of gyration (Rg), root mean square fluctuation (RMSF) and secondary structural elements including α-helices, sheets and turns between wild-type (WT) and mutant forms of COMT protein. In conclusion, our study provides novel insights into the deleterious effects and impact of V158M mutation on COMT protein structure which plays a key role in PTSD.
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影响因子：
10.3
作者：
Badour, Christal L.;Hirsch, R. Louis;Wang, Zhewu
通讯作者：
Wang, Zhewu
DOI：
10.1142/s0219720008003618
发表时间：
2008-08-01
影响因子：
1
作者：
Galzitskaya, Oxana V.;Bogatyreva, Natalya S.;Ivankov, Dmitry N.
通讯作者：
Ivankov, Dmitry N.
影响因子：
8
作者：
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通讯作者：
Hansmann, Ulrich H. E.
影响因子：
3.8
作者：
Gupta, Manoj Kumar;Gouda, Gayatri;Behera, Lambodar
通讯作者：
Behera, Lambodar
影响因子：
10.3
作者：
Amstadter, Ananda B.;Koenen, Karestan C.;Gelernter, Joel
通讯作者：
Gelernter, Joel