Hydration structure and stability of Met-enkephalin studied by a three-dimensional reference interaction site model with a repulsive bridge correction and a thermodynamic perturbation method

We study the hydration structure and free energy of several conformations o f Met-enkephalin in ambient water by employing the one-dimensional (1D) as well as three-dimensional (3D) reference interaction site model (RISM) inte gral equation theories, complemented by the hypernetted chain (HNC) closure with the repulsive bridge correction (RBC). The RBC contribution to the ex cess chemical potential of solvation is calculated by means of the thermody namic perturbation theory (TPT), which crucially reduces computational burd en and thus is especially important for a hybrid algorithm of the RISM with molecular simulation. The 3D-RISM/HNC+RBC-TPT approach provides improved p rediction of the solvation thermodynamics and gives a detailed description of the solvation structure of a biomolecule. The results obtained are discu ssed and compared to those following from the 1D-RISM/HNC theory. The latte r yields physically reasonable results for the conformational stability of biomolecules in solution, which is further improved by adding the 1D-RBC. T he modified, 1D-RISM/HNC+RBC-TPT integral equation theory combined with the simulated annealing or generalized-ensemble Monte Carlo simulation methods is capable of reliable prediction of conformations of biomolecules in solu tion with due account for the solvent effect at the microscopic level. (C) 2000 American Institute of Physics. [S0021-9606(00)50845-9].