Helix folding of an alanine-based peptide in explicit water

Computer simulations using full atomic representations for both the peptide and water molecules were performed to study the folding of a 16-residue al anine-based helical peptide in aqueous solution. Using a recently developed self-guided molecular dynamics (SGMD) method, which was shown to improve t he conformational searching efficiency significantly as compared to convent ional MD simulation method, reversible folding (folding, unfolding and refo lding) of a 16-residue alanine-based synthetic peptide in explicit water at 274 K was successfully accomplished. Consistent with experimental results, the helix was found to be the major secondary structural element in aqueou s solution, and among different helix forms, the a-helix is the dominant fo rm. Conformational analysis of our simulation results showed that turns and 3(10)-helices play an essential-role in the folding of cr-helix. Interesti ngly, our results showed that the propagation of a helix segment is more fr equent at the C-end than at the N-end. In most helix conformations, the bac kbone carbonyl groups of the peptide prefer to simultaneously form intramol ecular hydrogen bonds with the backbone amide groups of the peptide and int ermolecular hydrogen bonds with water molecules, indicating water accessibi lity to the backbone carbonyl groups is crucial for helix formation in wate r. Therefore, the helical propensities of amino acids may be related to the water accessibility of their backbone groups in helical conformation. Wate r molecules also function as hydrogen bonding-bridges linking helical resid ue pairs (i, i + n, with n = 3, 4, 5), suggesting a role of water bridges i n helix folding.