Assessing side-chain perturbations of the protein backbone: A knowledge-based classification of residue Ramachandran space Journal Article


Authors: Dahl, D. B.; Bohannan, Z.; Mo, Q.; Vannucci, M.; Tsai, J.
Article Title: Assessing side-chain perturbations of the protein backbone: A knowledge-based classification of residue Ramachandran space
Abstract: Grouping the 20 residues is a classic strategy to discover ordered patterns and insights about the fundamental nature of proteins, their structure, and how they fold. Usually, this categorization is based on the biophysical and/or structural properties of a residue's side-chain group. We extend this approach to understand the effects of side chains on backbone conformation and to perform a knowledge-based classification of amino acids by comparing their backbone φ{symbol},ψ distributions in different types of secondary structure. At this finer, more specific resolution, torsion angle data are often sparse and discontinuous (especially for nonhelical classes) even though a comprehensive set of protein structures is used. To ensure the precision of Ramachandran plot comparisons, we applied a rigorous Bayesian density estimation method that produces continuous estimates of the backbone φ{symbol},ψ distributions. Based on this statistical modeling, a robust hierarchical clustering was performed using a divergence score to measure the similarity between plots. There were seven general groups based on the clusters from the complete Ramachandran data: nonpolar/β-branched (Ile and Val), AsX (Asn and Asp), long (Met, Gln, Arg, Glu, Lys, and Leu), aromatic (Phe, Tyr, His, and Cys), small (Ala and Ser), bulky (Thr and Trp), and, lastly, the singletons of Gly and Pro. At the level of secondary structure (helix, sheet, turn, and coil), these groups remain somewhat consistent, although there are a few significant variations. Besides the expected uniqueness of the Gly and Pro distributions, the nonpolar/β-branched and AsX clusters were very consistent across all types of secondary structure. Effectively, this consistency across the secondary structure classes implies that side-chain steric effects strongly influence a residue's backbone torsion angle conformation. These results help to explain the plasticity of amino acid substitutions on protein structure and should help in protein design and structure evaluation. © 2008 Elsevier Ltd. All rights reserved.
Keywords: protein conformation; protein localization; proteins; bayes theorem; serine; tyrosine; amino acid sequence; isoleucine; threonine; alanine; amino acids; protein folding; protein secondary structure; leucine; protein structure, secondary; glutamine; methionine; lysine; glycine; arginine; histidine; phenylalanine; valine; tryptophan; proline; mathematical analysis; clustering; bayesian density estimation; ramachandran plot; residue backbone similarity; torsion angles; cystine; ramachandran
Journal Title: Journal of Molecular Biology
Volume: 378
Issue: 3
ISSN: 0022-2836
Publisher: Academic Press Inc., Elsevier Science  
Date Published: 2008-05-02
Start Page: 749
End Page: 758
Language: English
DOI: 10.1016/j.jmb.2008.02.043
PUBMED: 18377931
PROVIDER: scopus
PMCID: PMC2440669
DOI/URL:
Notes: --- - "Cited By (since 1996): 12" - "Export Date: 17 November 2011" - "CODEN: JMOBA" - "Source: Scopus"
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  1. Qianxing Mo
    37 Mo