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

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 simulations were completed starting from an initial conformational α-helix and an irregular structure, respectively. Each replica was run for 300 ns. 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-syn12 peptide in water adopted four different conformational states: the first state was a β-hairpin ensemble with Turn(9-6) and four hydrogen bonds, the second state was a β-hairpin ensemble with two turns (Turn(9-6) and Turn(5-2)) and three hydrogen bonds, the third state was a disordered structure with both Turn(8-5) and Turn(5-2), 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-hairpin 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-syn12 peptide in water by T-REMD.