Measurements of protein sequence–structure correlations

Correlations between protein structures and amino acid sequences are widely used for protein structure prediction. For example, secondary structure predictors generally use correlations between a secondary structure sequence and corresponding primary structure sequence, whereas threading algorithms and similar tertiary structure predictors typically incorporate interresidue contact potentials. To investigate the relative importance of these sequence-structure interactions, we measured the mutual information among the primary structure, secondary structure and side-chain surface exposure, both for adjacent residues along the amino acid sequence and for tertiary structure contacts between residues distantly separated along the backbone. We found that local interactions along the amino acid chain are far more important than non-local contacts and that correlations between proximate amino acids are essentially uninformative. This suggests that knowledge-based contact potentials may be less important for structure predication than is generally believed.