An automatic method for assessing structural importance of amino acid positions
1 Computer Science Department, University College London, Gower St, London, WC1E 6BT, UK
2 Division of Mathematical Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK
BMC Structural Biology 2009, 9:10 doi:10.1186/1472-6807-9-10Published: 4 March 2009
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.
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.
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.