Thermodynamic Parameters for the Helix-Coil Transition of Oligopeptides: Molecular Dynamics Simulation With the Peptide Growth Method

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-11, Vol.92 (24), p.10924-10928
• Main Authors: Wang, Lu, O'Connell, Thomas, Tropsha, Alexander, Hermans, Jan
• Format: Article
• Language: English
• Subjects: Alanine; Amino acids; Atoms; Biochemistry; Biophysics; Free energy; Molecular dynamics; Molecules; Oligomers; Oligopeptides - chemistry; Protein Structure, Secondary; Simulations; Thermodynamics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.24.10924

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 α-helical conformation. The key 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., α-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 σ and s parameters for helix initiation and helix growth. The calculated σ and s parameters for the polyalanine α-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.