title: Structural constraints on the covariance matrix derived from multiple aligned protein sequences.
abstract: Residue contact predictions were calculated based on the mutual information observed between pairs of positions in large multiple protein sequence alignments. Where previously only the statistical properties of these data have been considered important, we introduce new measures to impose constraints that make the contact map more consistent with a three dimensional structure. These included global (bulk) properties and local secondary structure properties. The latter allowed the contact constraints to be employed at the level of filtering pairs of secondary structure contacts which led to a more efficient (lower-level) implementation in the PLATO structure prediction server. Where previously the measure of success with this method had been whether the correct fold was predicted in the top 10 ranked models, with the current implementation, our summary statistic is the number of correct folds included in the top 10 models--which is on average over 50 percent.
authors.affiliation: Division of Mathematical Biology, MRC National Institute for Medical Research, London, United Kingdom. wtaylor@nimr.mrc.ac.uk
authors.forename: William R
authors.initials: WR
authors.lastname: Taylor
authors.forename: Michael I
authors.initials: MI
authors.lastname: Sadowski
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D030562:Databases, Protein; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment / Q000379:methods*
chemical_list: D000596:Amino Acids; D011506:Proteins