Studies on free energy calculations. I. （研究自由能计算。）.pdf

Studies on free energy calculations. I. Thermodynamic integration using a polynomial path Haluk Resat and Mihaly Mezei Department of Physiology and Biophysics, Mount Sinai School of Medicine, CUNY, New York, New York 10029-6574 (Received 26 April 1993; accepted 2 July 1993) The difference in the free energy of hydration between the C, and aR conformations of alanine dipeptide at infinite dilution is computed using Monte Carlo method in a canonical ensemble with the united-atom AMBER force field. The recently introduced polynomial path with dif- ferent exponents for the calculation of liquid state free energies using thermodynamic integration (TI) is tested. This is achieved by separating the interaction energy between the solute and the solvent molecules into the constituent r-l*, r-’ and Coulomb terms. The separate contribution of each term is calculated and the comparison shows that the shape of the TI integrand as a function of the coupling parameter is mainly determined by the Coulomb term. Analysis of the convergence characteristics shows that five-point Gaussian quadrature integration would be sufficient to obtain quantitatively reliable results when a polynomial path is employed. I. INTRODUCTION factors are also important in speeding up the numerical calculations. Since