parameters of hydration of peptide

A method is described for the inclusion of the effects of hydration in empirical conformational energy com- putations on polypeptides. The free energy of hydration is composed of additive contributions of various functional groups. The hydration of each group is assumed to be propor- tional to the accessible surface area of the group. The constants of proportionality, representing the free energy of hydration per unit area of accessible surface, have been evaluated for seven classes of groups (occurring in peptides) by least-squares fitting to experimental free energies of solution of small monofunctional aliphatic and aromatic molecules. The same method has also been applied to the modeling of the enthalpy and heat capacity of hydration, each of which is computed from the accessible surface area. The free energy of folding of a protein consists of the sum of contributions from the energy of its intramolecular interac- tions (1, 2) and from the free energy of interaction of the molecule with the surrounding solvent water. Exact compu- tation of the latter contribution still poses problems (3). As a practical approach, hydration-shell models have been used. In these models, the free energy of interaction of water molecules with the solute is expressed in the form of an averaged effective potential of interaction of atoms (and functional groups) of a solute molecule with a layer of solvent around each atom (4-10)-i.e., in terms of a potential of mean force (3). An empirical free energy of hydration is assigned to every atom and group. When the conformation of the protein changes, some water is eliminated from the hydration shell whenever groups on the protein approach each other. The free energy change accompanying this process depends on the total free energy of hydration of the groups and on the amount of water being eliminated from the hydration shells. This amount, in turn, depends on the size and distance of separation of the groups that approach each other, and it can be computed by geometrical methods from the volumes of overlapping spheres (4-6, 10, 11). The hydration-shell model contains several approxima- tions, which may be sources of error and also reduce the speed of computer-based numerical computations (8), such as the thickness of the shell, the apportioning of the free energy between overlapping hydration shells of covalently connected atoms, and the calculation of the volume of overlap of three or more hydration spheres that belong to nearby atoms. The latter problem can be overcome, howev- er, by modifying the computing procedures (10, 11). We have initiated an alternative approach, in order to avoid these problems. We assume that the extent of interaction of any functional group i of a solute with the solvent is