Structure and Thermodynamic Properties of Aqueous Solutions of Small Molecules and Proteins

Ab4'uci.t — The structures and reactivities of proteins are markedly influenced by water. In conformational energy calculations, the hydration of proteins is treated by a hydration-shell model. Originally, the shell model was parameterized with exoerimental data, but more recently empirical potentials were introduced to obtain these parameters by Monte Carlo and molecular dynamics techniques. These simulation methods are being used to obtain structural, dynamic and thermodynamic properties of liquid water and aqueous solutions of nonpolar and polar solutes. Calculations have also been carried out on aqueous solutions containing more than one solute molecule, e.g., several nonpolar molecules to investigate the hydrophobic interaction. An array processor, supported by a minicomputer host, has made it possible to treat large systems and to make long runs in Monte Carlo and molecular dynamics simulations. Nevertheless, problems still remain in obtaining convergence to the proper thermodynamic limit and in computing free energies and entropies of hydration. This paper is concerned with the history of these developments and with the roblems that remain to be solved in order to provide an accurate treatment of the effect of water on protein structure and reactivity.