Hydration free energy of hydrophobic solutes studied by a reference interaction site model with a repulsive bridge correction and a thermodynamic perturbation method

We modify the site-site as well as three-dimensional (3D) versions of the r eference interaction site model (RISM) integral equations with the hypernet ted chain (HNC) closures by adding a repulsive bridge correction (RBC). The RBC treats the overestimation of water ordering around a hydrophobic solut e in the RISM/HNC approximation, and thus refines the entropic component in the hydration free energy. We build up the bridge functions on r(-12) repu lsive core potentials, and propose RBC expressions for both the site-site a nd 3D-RISM approaches. To provide fast calculation, we obtain the excess ch emical potential of hydration by using the thermodynamic perturbation theor y (TPT). The site-site RISM/HNC+RBC as well as 3D-RISM/HNC+RBC approaches a re applied to calculate the structure and thermodynamics of hydration of ra re gases and alkanes in ambient water. For both approaches, the RBC drastic ally improves the agreement of the hydration chemical potential with simula tion data and provides its correct dependence on the solute size. For solut es of a nonspherical form, the 3D treatment yields the hydration structure in detail and better fits simulation results, whereas the site-site approac h is essentially faster. The TPT approximation gives the hydration thermody namics in good qualitative agreement with the exact results of the thermody namic integration, and substantially reduces computational burden. The RBC- TPT approximation can improve the predictive capability of the hybrid algor ithm of a generalized-ensemble Monte Carlo simulation combined with the sit e-site RISM theory, used to describe protein folding with due account for t he water effect at the microscopic level. The RBC can be optimized for bett er fit to reference simulation data, and can be generalized for solute mole cules with charged groups. (C) 2000 American Institute of Physics. [S0021-9 606(00)51031-9].