Proteins perform essential biochemical functions in and around living cells. Both the structure and function of each protein is coupled to its most proximate solvent layers, which describe the hydration shell. The physicochemical properties of hydration shell waters are distinct from bulk solution due to these coupled interactions. Whether hydration shells include additional hydration species besides water is one of the prevailing questions of protein chemistry and has far-reaching implications for accurate modeling of proteins. Coordinated solvent molecules can be observed at protein surfaces in neutron diffraction and X-ray crystallography experiments, and in high-resolution (~1 Å) experiments the confidence in the predicted coordinates for these solvent molecules is on par with the predicted coordinates for the protein atoms.<br/>Based on analyses of protein and water atom proximities in nearly 4000 high-resolution structures in the Protein Data Bank, we have identified tens of thousands of high-occupancy solvent molecules at protein surfaces. Many of these high-occupancy solvent molecules show interatomic distances comparable to those of protonated water clusters. Our findings indicate that solvent molecules coordinate around specific protein moieties, form large oligomeric clusters, and even exhibit sequence-specific coordination in homologous proteins. We also find that the orientations of hydrogen atoms from neutron diffraction experiments help explain many examples of coordinated solvent molecules in X-ray crystallography experiments.<br/>From these findings we propose that the solvent molecules observed in experimentally-characterized protein structures are necessary components of protein hydration shells that detail the essential coupled features of proteins with solution. Further, our observations provide a means to improve experimental and computational characterization of predicted protein structures.

Hydration at the protein surface: Observations from high-resolution data

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.