Comparison between the φ Distribution of the Amino Acids in the Protein Database and NMR Data Indicates that Amino Acids have Various φ Propensities in the Random Coil Conformation

Abstract

It has been indicated that amino acids have various intrinsic φ and ψ propensities, as demonstrated from the comparison between experimental secondary structure propensities and their relative statistical distribution in the protein database for the appropriate region of the Ramachandran plot. However, this does not eliminate the possibility that these experimental propensities are the result of context effects due to the secondary structure environment of the mutated position. To demonstrate that there are at least real intrinsic φ propensities, independent of context effects, we have used two different nuclear magnetic resonance parameters related to the φ dihedral angle ( J 3 αHNcoupling constants and the chemical shift of the C αH proton), determined in random-coil tetra- and pentapeptides, and/or in proteins. Comparison of the experimentally determined values for these parameters with the theoretical ones determined from the analysis by different empirical and theoretical equations of the φ dihedral angle statistical distribution of the amino acids in the protein database, supports the idea that each amino acid has, at least, different φ intrinsic propensities. Consideration of all conformations, or only coil conformations, in the protein database produces similar results. The reasonable correlation between these experimental and theoretical data and the hydrogen- exchange data in random-coil peptides suggests that maximisation of hydrophobic surface-buried and hydrogen-bond formation with the solvent could be responsible for these different random-coil conformational preferences. Analysis of the intrinsic propensities for β-strand, α-helix and polyproline II dihedral angles of the 20 amino acids in coil conformations, indicates that the side-chain of the amino acids is mainly determining the relative preferences for the φ angle.