Identification of SNPs in hMSH3/MSH6 interaction domain affecting the structure and function of MSH2 protein,Biotechnology and Applied Biochemistry

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Identification of SNPs in hMSH3/MSH6 interaction domain affecting the structure and function of MSH2 protein
Biotechnology and Applied Biochemistry ( IF 3.2 ) Pub Date : 2021-11-27 , DOI: 10.1002/bab.2295
Sidhartha Singh ₁ , Siddharth Sharma ₁ , Manoj Baranwal ₁

Affiliation

MutS homolog 2 (MSH2) is a mismatch repair gene that plays a critical role in DNA repair pathways, and its mutations are associated with different cancers. The present study aimed to find out the single nucleotide polymorphisms (SNPs) of MSH2 protein associated with causing structural and functional changes leading to the development of cancer with the help of computational tools. Four different tools for predicting deleterious SNPs (SIFT, PROVEAN, PANTHER, and PolyPhen), two tools each for identifying disease association (PhD-SNP and SNP&GO) and estimating stability (I-mutant and MUPro) were employed. Homology modeling, energy minimization, and root mean square deviation calculation were used to estimate structural variations. Twenty-seven SNPs and five SNPs (double amino acid change) were identified based on a consensus approach that might be associated with the structural and functional change in MSH2 protein. Molecular docking reveals that six SNPs affect the interaction of MSH2 and MSH6. Twelve identified SNPs were reported to be linked with hereditary nonpolyposis, colorectal cancer, and Lynch syndrome. Further, selected SNPs need to be validated in an in vitro system for their precise association with cancer predisposition.

中文翻译：

鉴定影响MSH2蛋白结构和功能的hMSH3/MSH6相互作用域中的SNP

MutS 同系物 2 (MSH2) 是一种错配修复基因，在 DNA 修复途径中起着关键作用，其突变与不同的癌症相关。本研究旨在借助计算工具找出与导致癌症发展的结构和功能变化相关的 MSH2 蛋白的单核苷酸多态性 (SNP)。使用了四种不同的预测有害 SNP 的工具（SIFT、PROVEAN、PANTHER 和 PolyPhen），两种工具分别用于识别疾病关联（PhD-SNP 和 SNP&GO）和估计稳定性（I-mutant 和 MUPro）。同源建模、能量最小化和均方根偏差计算用于估计结构变异。基于可能与 MSH2 蛋白的结构和功能变化相关的共识方法，确定了 27 个 SNP 和 5 个 SNP（双氨基酸变化）。分子对接揭示了六个 SNP 影响 MSH2 和 MSH6 的相互作用。据报道，已确定的 12 个 SNP 与遗传性非息肉病、结直肠癌和林奇综合征有关。此外，需要在体外系统中验证选定的 SNP 与癌症易感性的精确关联。

更新日期：2021-11-27

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