Hydration of peptides. II. Determination of the preferred sites of interactions of a cyclic dipeptide with water

As a first step in the determination of the hydration scheme of small peptides, the hydration sites of the cyclic dipeptide c(l-Thr-l-His) have been determined by two empirical potential treatments. In the first approach the energy is calculated by using the “Caillet-Claverie's” potentials, including electrostatic, dispersion-repulsion and polarization contributions. In the second approach (EMPWI method), the energy is calculated by simplified treatment, taking into account the electrostatic interactions of a suitable charge distribution and the dispersion-repulsion contributions. In this study, only the crystalline conformation of the cyclic dipeptide is considered. The hydration sites determined can be classified in three groups: (a) bridging sites, in which water interacts with both side chains, (b) bridging sites in which water interacts with one side chain and the DKP ring, (c) individual sites in which water interacts only with one polar group. The agreement between the results obtained by the two calculations is sufficiently satisfactory. This allows us to use EMPWI potential for calculations of more complex systems.