PROTEIN HYDRATION OBSERVED BY X-RAY-DIFFRACTION - SOLVATION PROPERTIES OF PENICILLOPEPSIN AND NEURAMINIDASE CRYSTAL-STRUCTURES

Solvation in macromolecular crystal structures was studied by analyzin g X-ray diffraction data of two proteins, penicillopepsin and neuramin idase. The quality of several solvent models was assessed by complete cross-validation in order to prevent overfitting the diffraction data. Radial solvent distribution functions were computed from electron den sity maps using phases obtained from multiple isomorphous replacement and from the protein's atomic model combined with the best solvent mod el. Distribution functions were computed around hydrophilic and hydrop hobic groups on the protein's surface. averaging of the distribution f unctions was performed in order to reduce the influence of noise. The first solvation shell is characterized by a peak in the average distri bution functions. At 1.8 Angstrom resolution, polar groups show a shar p peak while non-polar groups show a broad one. The distinction betwee n hydrophobic and hydrophilic solvation sites is lost when using lower resolution (2.8 Angstrom) diffraction data. Higher-order solvation sh ells are not observed in the average distribution functions. We hope t hat site-specific radial distribution functions obtained from high-qua lity diffraction data will produce a picture of macromolecular solvati on consistent with available experimental data and computational resul ts.