Structural and thermodynamics characters of isolated α-syn12 peptide： long-time temperature replica-exchange molecular dynamics in aqueous solution  

作　　者：Zanxia Cao Lei Liu Ping Wu Jihua Wang 

机构地区：[1]Key Lab of Biophysics in Universities of Shandong, Dezhou 253023, China [2]Department of Physics, Dezhou University, Dezhou 253023, China [3]Department of Computer Science and Technology, Dezhou University, Dezhou 253023, China [4]Department of Chemistry, Dezhou University, Dezhou 253023, China

出　　处：《Acta Biochimica et Biophysica Sinica》2011年第3期172-180,共9页生物化学与生物物理学报（英文版）

基　　金：Acknowledgement We would like to thank Prof. H.J.C. Berendsen （University of Groningen） for providing us with the GROMACS programs. Funding This work was supported by grants from the National Natural Science Foundation of China （30970561 and 31000324） and the Shandong Province Natural Science Foundation （2009ZRA 14027 and 2009ZRA 14028）.

摘　　要：The structural and thermodynamics characters of α-syn12 （residues 1-12 of the human α-synuclein protein） peptide in aqueous solution were investigated through temperature replica-exchange molecular dynamics （T-REMD） simulations with the GROMOS 43A1 force field. The two independent T-REMD simu- lations were completed starting from an initial conformational α-helix and an irregular structure, respectively. Each replica was run for 300ns. The structural and thermodynamics characters were studied based on parameters such as distributions of backbone dihedral angles, free energy surface, stability of folded β-hairpin structure, and favorite conformations. The results showed that the isolated α-synl2 peptide in water adopted four different conformational states： the first state was a β-hairpin ensemble with Turn9_6 and four hydrogen bonds, the second state was a IS-hairpin ensemble with two turns （Turn9_6 and Turns_e） and three hydrogen bonds, the third state was a disordered structure with both Turns_s and Turns_2, and the last state was a π-helix ensemble. Meanwhile, we studied the free energy change of α-syn12 peptide from the unfolded state to the β-bairpin state, which was in good agreement with the experiments and molecular dynamics simulations for some other peptides. We also analyzed the driving force of the peptide transition. The results indicated that the driving forces were high solvent exposure of hydrophobic Leu8 and hydrophobic residues in secondary structure. To our knowledge, this was the first report to study the isolated α-synl2 peptide in water by T-REMD.The structural and thermodynamics characters of α-syn12 （residues 1-12 of the human α-synuclein protein） peptide in aqueous solution were investigated through temperature replica-exchange molecular dynamics （T-REMD） simulations with the GROMOS 43A1 force field. The two independent T-REMD simu- lations were completed starting from an initial conformational α-helix and an irregular structure, respectively. Each replica was run for 300ns. The structural and thermodynamics characters were studied based on parameters such as distributions of backbone dihedral angles, free energy surface, stability of folded β-hairpin structure, and favorite conformations. The results showed that the isolated α-synl2 peptide in water adopted four different conformational states： the first state was a β-hairpin ensemble with Turn9_6 and four hydrogen bonds, the second state was a IS-hairpin ensemble with two turns （Turn9_6 and Turns_e） and three hydrogen bonds, the third state was a disordered structure with both Turns_s and Turns_2, and the last state was a π-helix ensemble. Meanwhile, we studied the free energy change of α-syn12 peptide from the unfolded state to the β-bairpin state, which was in good agreement with the experiments and molecular dynamics simulations for some other peptides. We also analyzed the driving force of the peptide transition. The results indicated that the driving forces were high solvent exposure of hydrophobic Leu8 and hydrophobic residues in secondary structure. To our knowledge, this was the first report to study the isolated α-synl2 peptide in water by T-REMD.

关 键 词：α-synl2 temperature replica exchange molecular dynamics simulation free energy surface 

分 类 号：Q78[生物学—分子生物学] TG111.4[金属学及工艺—物理冶金]