title: Effect of pH on the Aggregation of α-syn12 Dimer in Explicit Water by Replica-Exchange Molecular Dynamics Simulation.
abstract: The dimeric structure of the N-terminal 12 residues drives the interaction of α-synuclein protein with membranes. Moreover, experimental studies indicated that the aggregation of α-synuclein is faster at low pH than neutral pH. Nevertheless, the effects of different pH on the structural characteristics of the α-syn12 dimer remain poorly understood. We performed 500 ns temperature replica exchange molecular dynamics (T-REMD) simulations of two α-syn12 peptides in explicit solvent. The free energy surfaces contain ten highly populated regions at physiological pH, while there are only three highly populated regions contained at acidic pH. The anti-parallel β-sheet conformations were found as the lowest free energy state. Additionally, these states are nearly flat with a very small barrier which indicates that these states can easily transit between themselves. The dimer undergoes a disorder to order transition from physiological pH to acidic pH and the α-syn12 dimer at acidic pH involves a faster dimerization process. Further, the Lys6-Asp2 contact may prevent the dimerization.
authors.affiliation: Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Dezhou 253023, China. qiayilai@mail.ustc.edu.cn.|College of Physics and Electronic information, Dezhou University, Dezhou 253023, China. qiayilai@mail.ustc.edu.cn.
authors.forename: Zanxia
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Dezhou 253023, China. zhangxiumei@dzu.edu.cn.|College of Physics and Electronic information, Dezhou University, Dezhou 253023, China. zhangxiumei@dzu.edu.cn.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Computer Science and Technology, Dezhou University, Dezhou 253023, China. leiliusid@gmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Dezhou 253023, China. zhaoll@sina.com.|College of Physics and Electronic information, Dezhou University, Dezhou 253023, China. zhaoll@sina.com.
authors.forename: Liling
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Dezhou 253023, China. tianwaifeixian78@163.com.|College of Physics and Electronic information, Dezhou University, Dezhou 253023, China. tianwaifeixian78@163.com.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Dezhou 253023, China. jhw25336@126.com.|College of Physics and Electronic information, Dezhou University, Dezhou 253023, China. jhw25336@126.com.
authors.forename: Jihua
authors.initials: J
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D051844:alpha-Synuclein
keywords: different pH; dimerization; molecular dynamics simulation; structural character; α-synuclein