The structure of a protein can be analysed in terms of what may be called the “hydrophobic moments” of (1) the entire molecule and (2) of the segments of secondary structure that make up the polypeptide chain. The zeroth moment is defined as the sum of the hydrophobicities of the amino-acid residues of the structure under consideration; it is the analogue of the net charge of a cluster of point charges. The first moment, or hydrophobic dipole moment, is the analogue of the electric dipole moment of a cluster of charges. Just as the electric dipole moment measures the asymmetry of the charge distribution, the hydrophobic dipole moment measures the amphiphilicity (asymmetry of hydrophobicity) of the structure. A large hydrophobic dipole moment indicates that a structure is predominantly hydrophobic on one side and predominantly hydrophilic on the other. A quadrupole hydrophobic moment may be similarly defined. It indicates whether a protein is more hydrophobic in its interior (as for a globular protein in aqueous solution) or at its surface (as for a membrane protein).

The hydrophobic dipole moment is useful in two separate applications. The first, which we have discussed elsewhere [D. Eisenberg, R. M. Weiss and T. C. Terwilliger, Nature (London), 1982, 299, 371] relates the function and secondary structure of a region of protein structure to its amino-acid sequence. For example, sequences that form surface-seeking helices have large hydrophobic dipole moments. The second application is in the analysis of interactions of a segment or domain of a protein with neighbouring regions in the protein and with other parts of the environment. In this paper we examine the hydrophobic dipole moments in the known structures of nine globular proteins and find that the moments of neighbouring segments tend to point towards each other. This suggests that the hydrophobic dipole can serve as a simple and pictorial summary of some of the forces at work in the folding of proteins. We have also found that the interactions of some macromolecules with an apolar–polar interface can be conveniently described in terms of the hydrophobic moments of the molecule and a “hydrophobic field” which reflects the hydrophobicity of the environment.