Solvent effects on the conformational transition of a model polyalanine peptide

We have investigated the folding of polyalanine by combining discontinuous molecular dynamics simulation with our newly developed off‐lattice intermediate‐resolution protein model. The thermodynamics of a system containing a single Ac‐KA 14 K‐NH 2 molecule has been explored by using the replica exchange simulation method to map out the conformational transitions as a function of temperature. We have also explored the influence of solvent type on the folding process by varying the relative strength of the side‐chain's hydrophobic interactions and backbone hydrogen bonding interactions. The peptide in our simulations tends to mimic real polyalanine in that it can exist in three distinct structural states: α‐helix, β‐structures (including β‐hairpin and β‐sheet–like structures), and random coil, depending upon the solvent conditions. At low values of the hydrophobic interaction strength between nonpolar side‐chains, the polyalanine peptide undergoes a relatively sharp transition between an α‐helical conformation at low temperatures and a random‐coil conformation at high temperatures. As the hydrophobic interaction strength increases, this transition shifts to higher temperatures. Increasing the hydrophobic interaction strength even further induces a second transition to a β‐hairpin, resulting in an α‐helical conformation at low temperatures, a β‐hairpin at intermediate temperatures, and a random coil at high temperatures. At very high values of the hydrophobic interaction strength, polyalanines become β‐hairpins and β‐sheet–like structures at low temperatures and random coils at high temperatures. This study of the folding of a single polyalanine‐based peptide sets the stage for a study of polyalanine aggregation in a forthcoming paper.