FAVORED AND SUPPRESSED PATTERNS OF HYDROPHOBIC AND NONHYDROPHOBIC AMINO-ACIDS IN PROTEIN SEQUENCES

Hydrophobic amino acids of the group Leu, Ile, Val, Phe, and Met (LIVF M) are distributed in favored or suppressed patterns within protein se quences. The frequencies of all rive-position combinations of lozenge = LIVFM and lozenge = non-LIVFM residues were analyzed in 48 proteins of known crystallographic structure. Some motifs were strongly preferr ed or suppressed; e.g., lozenge was favored (z = 3.5), while lozenge w as suppressed (z = -3.4). In longer patterns, lozenge followed by loze nge and one lozenge was favored (lozenge, z = 5.1), while conversion o f the single hydrophobic residue to a pair was not (lozenge, z = 0.8). Distributions of certain non-LIVFM amino acids around lozenge positio ns in strongly favored patterns were also favored or disfavored (Asp, Glu, Lys, Arg, Asn, Cys, Tyr, and Pro; for each Absolute value of z > 2.0). While the strongly favored pattern lozenge was found in both alp ha-helical and beta-strand sequences, it associated significantly with alpha-helices (z = 3.6 for the second-position alpha-helical phi and psi angles) but not with beta-strands (z = -1.1). Certain motifs of LI VFM and non-LIVFM residues might be selected if they lead efficiently to the local nucleations hypothesized to characterize molten globule i ntermediates in the folding of proteins.