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通过 MD 模拟研究揭示 DACH1 受体在癌侵袭发展中的作用机制。

Mechanistic insight of DACH1 receptor in the development of carcinoma insurgence through MD simulation studies.

机构信息

Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan.

Institute of Molecular Sciences and Bioinformatics, Lahore, Pakistan.

出版信息

J Biomol Struct Dyn. 2022 Feb;40(2):742-751. doi: 10.1080/07391102.2020.1818624. Epub 2020 Sep 14.

DOI:10.1080/07391102.2020.1818624
PMID:32924784
Abstract

Proteins are key player in the prognosis and therapeutics of carcinomas through the interactions of downstream signalling cascades. Current work insight the structural and mutational analysis of DACH1 in association with carcinogenesis. The homology modelling was employed to predict mutant and wild protein models and their reliability and accuracy was verified through multiple online approaches. Furthermore, MD simulation technique was employed to check the mutation effects on the stability of DACH1 through root mean square deviation and fluctuation graphs. Our results proposed that DACH1 mutation (C188Y) may cause lethal effects and can disturb the DACH1 structure. The observed mutational results showed that C188Y may cause some lethal effect in human body. Based on aforementioned computational assessments, it has concluded that DACH1 could be used as good therapeutic target in the prognosis and therapeutic of carcinoma insurgence.Communicated by Ramaswamy H. Sarma.

摘要

蛋白质通过下游信号级联的相互作用,成为癌预后和治疗的关键因素。目前的研究深入探讨了 DACH1 与癌变相关的结构和突变分析。同源建模被用来预测突变和野生蛋白模型,通过多种在线方法验证了它们的可靠性和准确性。此外,MD 模拟技术被用来通过均方根偏差和波动图检查突变对 DACH1 稳定性的影响。我们的研究结果表明,DACH1 突变(C188Y)可能导致致命效应,并可能扰乱 DACH1 结构。观察到的突变结果表明,C188Y 可能在人体内产生一些致命影响。基于上述计算评估,我们得出结论,DACH1 可作为癌发生预后和治疗的良好治疗靶点。通讯作者:Ramaswamy H. Sarma。

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