Chiral Ramachandran Plots I: Glycine

Abstract

Ramachandran plots (RPs) map the wealth of conformations of the polypeptide backbone and are widely used to characterize protein structures. A limitation of the RPs is that they are based solely on two dihedral angles for each amino acid residue and provide therefore only a partial picture of the conformational richness of the protein. Here we extend the structural RP analysis of proteins from a two-dimensional (2D) map to a three-dimensional map by adding the quantitative degree of chirality-the continuous chirality measure (CCM)-of the amino acid residue at each point in the RP. This measure encompasses all bond angles and bond lengths of an amino acid residue. We focus in this report on glycine (Gly) because, due to its flexibility, it occupies a large portion of the 2D map, thus allowing a detailed study of the chirality measure, and in order to evaluate the justification of classically labeling Gly as the only achiral amino acid. We have analyzed in detail 4366 Gly residues extracted from high resolution crystallographic data of 160 proteins. This analysis reveals not only that Gly is practically always conformationally chiral, but that upon comparing with the backbone of all amino acids, the quantitative chirality values of Gly are of similar magnitudes to those of the (chiral) amino acids. Structural trends and energetic considerations are discussed in detail. Generally we show that adding chirality to Ramachandran plots creates far more informative plots that highlight the sensitivity of the protein structure to minor conformational changes.

Side chain flexibility and the symmetry of protein homodimers

“…However, other than the sample size (the number of general residues is much larger than that of Gly, Pro or Pre-Pro), no significant differences emerged in the spread of the CCM values that could be attributed to the type of the Ramachandran group. Notably, despite its description as the only achiral amino acid, Gly is chiral within the protein, with a CCM range of [0,5], consistent with previous studies [30]. Looking again at Table 1 and Fig 3, we can now claim that the S(C 2 ) values of the homodimers should be regarded as a common CSM scale for proteins with approximate symmetry, although they represent only one aspect of the deviation from perfect symmetry.…”

“…Our in-house-designed Perl program, pdbslicer [ 30 ], was used to extract the complete subunit and the backbone subunit of 258,822 (= 129,411 × 2) residues from our main set and calculate their CCMs. The double-dimers set produced two sets of 19,679 residue pairs each, taken from the first and second dimer of each PDB file (78,716 residues in total).…”

“…Our in-house-designed Perl program, pdbslicer [30], was used to extract the complete subunit and the backbone subunit of 258,822 (= 129,411 × 2) residues from our main set and calculate…”

“…Another recent application of the CSM to protein structure is the addition of residue chirality as a third dimension of Ramachandran plots [30,31]. This addition has revealed hidden conformational information that improves the understanding and characterization of protein structure.…”

The near-symmetry of protein oligomers: NMR-derived structures

“…The CSM measure is a global parameter, and thus allows the comparison of various structures and various symmetries on the same scale. Numerous applications of the CSM methodology all across chemistry have been reported and few examples are collected in the cited references [27][28][29][30] , including biochemistry 14,31,32 and physics 33-37 . types of symmetry analysis. In previous studies 13, 14 we have introduced specific CSM computational tools for the evaluation of the symmetry content, S(G), of proteins.…”