文献类型：期刊文献

英文题名：Exploring the mechanism of a regulatory SNP of KLK3 by molecular dynamics simulation

作者：Zhang, Zhiyi[1,2];Liu, Ming[1,3,4];Li, Beiping[1];Wang, Yuelan[1];Yue, Junjie[1];Liang, Long[1];Sun, Jianzhong[2]

机构：[1]Beijing Inst Biotechnol, Beijing 100071, Peoples R China;[2]Beijing Inst Microbiol & Epidemiol, Beijing 100071, Peoples R China;[3]E China Univ Sci & Technol, Sch Biol Engn, Shanghai 200237, Peoples R China;[4]Genor Biopharma Co Ltd, Shanghai 201203, Peoples R China

年份：2013

卷号：31

期号：4

起止页码：426

外文期刊名：JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000316111300008)】；

语种：英文

外文关键词：KLK3; AR; rSNP; proteinDNA binding; recognition helix; molecular dynamics simulation; hydrophobic; relative motion

摘要：The SNP -158G>A of KLK3 has been validated as a regulatory SNP (rSNP) by molecular biology assays, but the mechanism of how it affects the binding of an androgen receptor (AR) homodimer with DNA is unclear. In the current study, molecular dynamics simulation was adopted to explain its inner cause. Based on a recent review), three types of intermolecular forces were analyzed, and the differences among them were compared between complexes containing -158 A:T and -158 G:C. Extra hydrophobic contacts caused by the methyl group on the mutated thymine were the most crucial factor to the regulatory effect of this rSNP. Further analysis concerning the relative motion of the two recognition helixes of the AR homodimer indicated that the hydrophobic interactions between the recognition helix B and the major groove containing -158 A:T changed that helix's motion greatly from swaying in a plane at free state to vibrating slightly around an equilibrium position. A relatively full explanation on the occurrence of rSNP -158G>A is presented here.