MODE MATCHES AND THEIR LOCATIONS IN THE HYDROPHOBIC FREE-ENERGY SEQUENCES OF PEPTIDE LIGANDS AND THEIR RECEPTOR EIGENFUNCTIONS

Patterns in sequences of amino acid hydrophobic bic free energies pred ict secondary structures in proteins. In protein folding, matches in h ydrophobic free energy statistical wavelengths appear to contribute to selective aggregation of secondary structures in ''hydrophobic zipper s.'' in a similar setting, the use of Fourier analysis to characterize the dominant statistical wavelengths of peptide ligands' and receptor proteins' hydrophobic modes to predict such matches has been limited blv the aliasing and end effects of short peptide lengths, as well as the broad-band, mode multiplicity of many of their frequency (power) s pectra. In addition. the sequence locations of the matching modes are lost in this transformation. We make new use of three techniques to ad dress these difficulties: (i) eigen-function construction from the lin ear decomposition of the lagged covariance matrices of the ligands and receptors as hydrophobic free energy sequences: (ii) maximum entropy, complex poles power spectra, which select the dominant modes of the h ydrophobic free energy sequences or their eigenfunctions; and (iii) di screte, best bases, trigonometric wavelet transformations, which confi rm the dominant spectral frequencies of the eigenfunctions and locate them as (absolute valued) moduli in the peptide or receptor sequence. The leading eigenfunction of the convariance matrix of a transmembrane receptor sequence locates the same transmembrane segments seen in n-b lock-averaged hydropathy plots whit leaving the remaining hydrophobic modes unsmoothed and available far further analysis as secondary eigen functions, In these receptor eigenfunctions, uf find a set: of statist ical wavelength matches between peptide ligands and their G-protein an d tyrosine kinase coupled receptors, ranging across examples from 13.1 0 amino acids in acid fibroblast growth factor to 2.18 residues in cor ticotropin releasing factor. We find that the wavelet-located receptor modes in the extracellular loops are compatible with studies of recep tor chimeric exchanges and point mutations. A nonbinding corticotropin -releasing factor receptor mutant is shown to have lost the signatory mode common to the normal receptor and its ligand. Hydrophobic free en ergy eigenfunctions and their transformations offer new quantitative p hysical homologies in database searches for peptide-receptor matches.