title: Exploring the mechanism of a regulatory SNP of KLK3 by molecular dynamics simulation.
abstract: 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.
authors.affiliation: Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Beiping
authors.initials: B
authors.lastname: Li
authors.forename: Yuelan
authors.initials: Y
authors.lastname: Wang
authors.forename: Junjie
authors.initials: J
authors.lastname: Yue
authors.forename: Long
authors.initials: L
authors.lastname: Liang
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Sun
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007610:Kallikreins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
chemical_list: C410798:AR protein, human; D009838:Oligodeoxyribonucleotides; D011944:Receptors, Androgen; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen