Simulations of the thermodynamic properties of a short polyalanine peptide using potentials of mean force

We report results of simulation studies of the equilibrium between helical and random coil states of dodeca-alanine by a method which systematically includes the effects of hydration. The statistical distribution of conformations at room temperature is determined and used to fit thermodynamic parameters for the helix to random coil equilibrium which may be directly compared with experimental data. The distribution of conformations is explored at atomic resolution by a constrained Langevin-dynamics simulated annealing technique which limits the effective number of degrees of freedom to two per residue. Water is included via a set of pair potentials of mean force. We show that the inclusion of hydration effects is essential for achieving a helical content comparable to that found experimentally. However, the cooperative nature of the helical state found in the simulations is low compared to the experimental value.