A ROLE FOR SURFACE HYDROPHOBICITY IN PROTEIN-PROTEIN RECOGNITION

The role of hydrophobicity as a determinant of protein-protein interac tions is examined. Surfaces of ape-protein targets comprising 9 classe s of enzymes, 7 antibody fragments, hirudin, growth hormone, and retin ol-binding protein, and their associated ligands with available X-ray structures for their complexed forms, are scanned to determine cluster s of surface-accessible amino acids. Clusters of surface residues are ranked on the basis of the hydrophobicity of their constituent amino a cids. The results indicate that the location of the co-crystallized li gand is commonly found to correspond with one of the strongest hydroph obic clusters on the surface of the target molecule. In 25 of 38 cases , the correspondence is exact, with the position of the most hydrophob ic cluster coinciding with more than one-third of the surface buried b y the bound ligand. The remaining 13 cases demonstrate this correspond ence within the top 6 hydrophobic clusters. These results suggest that surface hydrophobicity can be used to identify regions of a protein's surface most likely to interact with a binding ligand. This fast and simple procedure may be useful for identifying small sets of well-defi ned loci for possible ligand attachment.