THERMODYNAMIC PARAMETERS FOR THE HELIX-COIL TRANSITION OF OLIGOPEPTIDES - MOLECULAR-DYNAMICS SIMULATION WITH THE PEPTIDE GROWTH METHOD

The helix-coil transition equilibrium of polypeptides in aqueous solution was studied by molecular dynamics simulation, The peptide growth simulation method was introduced to generate dynamic models of polypeptide chains in a statistical (random) coil or an alpha-helical conformation, The keg element of this method is to build up a polypeptide chain during the course of a molecular transformation simulation, successively adding whole amino acid residues to the chain in a predefined conformation state (e.g., alpha-helical or statistical coil), Thus, oligopeptides of the same length and composition, but having different conformations, can be incrementally grown from a common precursor, and their relative conformational free energies can be calculated as the difference between the free energies for growing the individual peptides, This affords a straightforward calculation of the Zimm-Bragg sigma and s parameters for helix initiation and helix growth, The calculated sigma and s parameters for the polyalanine alpha-helix are in reasonable agreement with the experimental measurements. The peptide growth simulation method is an effective way to study quantitatively the thermodynamics of local protein folding.