Identification of Protein Surfaces and Interaction Sites by Hydrophilicity Analysis

Abstract

The packing of hydrophobic amino acids into the interior of proteins has been recognized as a major factor in the creation of a three dimensional structure from a linear amino acid sequence. A related realization is that regions of protein sequences that contain clusters of charged and polar amino acids are usually highly exposed at the protein surface, and are therefore likely to be involved in protein interactions with other molecules, for example, binding to antibodies. Long hydrophobic segments have been recognized as probable membrane spanning sequences. In 1981, we published a method for averaging the hydrophilicity values of the amino acids in protein sequences (Hopp and Woods, ref. 1). The hydrophilicity profiles made by this procedure are useful in locating antigenic sites on native protein antigens, because major antigenicity is always found in the highest peaks (1, 2). In 1982, Kyte and Doolittle (3) published a procedure that is virtually identical to ours, but made the additional observation that regions of wide hydrophobic maxima (valleys on our plots) are usually associated with membrane spanning segments of peptide chain. In this paper we compare our method to other similar procedures and describe several improvements to our method.