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An automatic method for assessing structural importance of amino acid positions.

Sadowski MI, Jones DT - BMC Struct. Biol. (2009)

Bottom Line: Some buried residues were found to be less informative than expected, particularly residues involved in active sites and the binding of small molecules.The correlation-based method generates predictions of structural importance for superfamily positions which agree well with previous results of manual analyses, and may be of use in automated residue annotation piplines.A PERL script which implements the method is provided.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computer Science Department, University College London, Gower St, London, WC1E 6BT, UK. msadows@nimr.mrc.ac.uk

ABSTRACT

Background: A great deal is known about the qualitative aspects of the sequence-structure relationship, for example that buried residues are usually more conserved between structurally similar homologues, but no attempts have been made to quantitate the relationship between evolutionary conservation at a sequence position and change to global tertiary structure. In this paper we demonstrate that the Spearman correlation between sequence and structural change is suitable for this purpose.

Results: Buried residues, bends, cysteines, prolines and leucines were significantly more likely to occupy positions highly correlated with structural change than expected by chance. Some buried residues were found to be less informative than expected, particularly residues involved in active sites and the binding of small molecules.

Conclusion: The correlation-based method generates predictions of structural importance for superfamily positions which agree well with previous results of manual analyses, and may be of use in automated residue annotation piplines. A PERL script which implements the method is provided.

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Related in: MedlinePlus

Improving sequence-structure correlations with strongly correlated positions: example with the globin superfamily. Spearman's rank correlations between sequence similarity scores calculated from subsets of alignment positions with TM-align RMSD scores are plotted for increasing subset size from left to right. Y-axis: correlation coefficient. Data are separated into close (> 30% identical) homologues (red lines) and distant homologues (blue lines). Thick lines depict the effect of adding positions in order of correlation from most to least; thin dashed lines show the effect of adding positions in reverse order. Dashed horizontal lines show correlations for full sequence identities for the distantly (upper line at -0.68) and closely (lower line at -0.73) related sets.
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Figure 3: Improving sequence-structure correlations with strongly correlated positions: example with the globin superfamily. Spearman's rank correlations between sequence similarity scores calculated from subsets of alignment positions with TM-align RMSD scores are plotted for increasing subset size from left to right. Y-axis: correlation coefficient. Data are separated into close (> 30% identical) homologues (red lines) and distant homologues (blue lines). Thick lines depict the effect of adding positions in order of correlation from most to least; thin dashed lines show the effect of adding positions in reverse order. Dashed horizontal lines show correlations for full sequence identities for the distantly (upper line at -0.68) and closely (lower line at -0.73) related sets.

Mentions: Figure 3 shows the rank correlations of sequence identity scores generated from subsets of increasing size with TM-align RMSD scores, using the globin sequences as an example. The data are split into close homologues (≥ 30% ID) and distant homologues (< 30%ID). For comparison the results of adding positions in reverse order are also plotted.


An automatic method for assessing structural importance of amino acid positions.

Sadowski MI, Jones DT - BMC Struct. Biol. (2009)

Improving sequence-structure correlations with strongly correlated positions: example with the globin superfamily. Spearman's rank correlations between sequence similarity scores calculated from subsets of alignment positions with TM-align RMSD scores are plotted for increasing subset size from left to right. Y-axis: correlation coefficient. Data are separated into close (> 30% identical) homologues (red lines) and distant homologues (blue lines). Thick lines depict the effect of adding positions in order of correlation from most to least; thin dashed lines show the effect of adding positions in reverse order. Dashed horizontal lines show correlations for full sequence identities for the distantly (upper line at -0.68) and closely (lower line at -0.73) related sets.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667441&req=5

Figure 3: Improving sequence-structure correlations with strongly correlated positions: example with the globin superfamily. Spearman's rank correlations between sequence similarity scores calculated from subsets of alignment positions with TM-align RMSD scores are plotted for increasing subset size from left to right. Y-axis: correlation coefficient. Data are separated into close (> 30% identical) homologues (red lines) and distant homologues (blue lines). Thick lines depict the effect of adding positions in order of correlation from most to least; thin dashed lines show the effect of adding positions in reverse order. Dashed horizontal lines show correlations for full sequence identities for the distantly (upper line at -0.68) and closely (lower line at -0.73) related sets.
Mentions: Figure 3 shows the rank correlations of sequence identity scores generated from subsets of increasing size with TM-align RMSD scores, using the globin sequences as an example. The data are split into close homologues (≥ 30% ID) and distant homologues (< 30%ID). For comparison the results of adding positions in reverse order are also plotted.

Bottom Line: Some buried residues were found to be less informative than expected, particularly residues involved in active sites and the binding of small molecules.The correlation-based method generates predictions of structural importance for superfamily positions which agree well with previous results of manual analyses, and may be of use in automated residue annotation piplines.A PERL script which implements the method is provided.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computer Science Department, University College London, Gower St, London, WC1E 6BT, UK. msadows@nimr.mrc.ac.uk

ABSTRACT

Background: A great deal is known about the qualitative aspects of the sequence-structure relationship, for example that buried residues are usually more conserved between structurally similar homologues, but no attempts have been made to quantitate the relationship between evolutionary conservation at a sequence position and change to global tertiary structure. In this paper we demonstrate that the Spearman correlation between sequence and structural change is suitable for this purpose.

Results: Buried residues, bends, cysteines, prolines and leucines were significantly more likely to occupy positions highly correlated with structural change than expected by chance. Some buried residues were found to be less informative than expected, particularly residues involved in active sites and the binding of small molecules.

Conclusion: The correlation-based method generates predictions of structural importance for superfamily positions which agree well with previous results of manual analyses, and may be of use in automated residue annotation piplines. A PERL script which implements the method is provided.

Show MeSH
Related in: MedlinePlus