Characterization of interfacial solvent in protein complexes and contribution of wet spots to the interface description.

Water networks in protein interfaces can complement direct interactions contributing significantly to molecular recognition, function, and stability of protein association. Thus, water can be seen as an extension or addition of protein structural features, which may add plenty of information to protein interfacial definition. However, solvent is frequently neglected in protein interaction studies. Analysis of the interfacial information contained in the PDB is essential to achieve more accurate descriptions of protein interfaces. With this aim, we have used the SCOWLP database (http://www.scowlp.org) and applied computational geometry methods to extract and analyze interfacial information of a high-resolution nonredundant dataset of 176 protein complexes containing obligate and transient interfaces. We have identified all interfacial residues and characterized them in terms of temperature factors, secondary structure, residue composition, and pairing preferences to understand their contribution to the interface description. We have paid special attention to water-bridged residues; focusing on those that interact only mediated by a water molecule called wet spots. Our results show that 40.1% of the interfacial residues are interacting through water and that wet spots represent a 14.5% of the total, emphasizing the importance of the inclusion of solvent in protein interaction studies, and the contribution of wet spots to interfacial description. Wet spots present similar characteristics to residues binding buried water molecules in the core or cavities of proteins; being preferably located in nonregular secondary structures and establishing hydrogen bonds by their main-chains. We observe that obligate and transient interfaces present a comparable amount of solvent. Moreover, the role of solvent in both complex types differs according to the different nature of their interfaces. The information obtained in our studies will assist in the process of accomplishing more accurate descriptions of protein interfaces and may be helpful to improve comparison of protein family interfaces, to facilitate rational ligand design, and to guide protein docking. 2007 Wiley-Liss, Inc.