Mutual information without the influence of phylogeny or entropy dramatically improves residue contact prediction.
BACKGROUND
Compensating alterations during the evolution of protein families give rise to coevolving positions that contain important structural and functional information. However, a high background composed of random noise and phylogenetic components interferes with the identification of coevolving positions.


RESULTS
We have developed a rapid, simple and general method based on information theory that accurately estimates the level of background mutual information for each pair of positions in a given protein family. Removal of this background results in a metric, MIp, that correctly identifies substantially more coevolving positions in protein families than any existing method. A significant fraction of these positions coevolve strongly with one or only a few positions. The vast majority of such position pairs are in contact in representative structures. The identification of strongly coevolving position pairs can be used to impose significant structural limitations and should be an important additional constraint for ab initio protein folding.


BACKGROUND
Alignments and program files can be found in the Supplementary Information.
Department of Biochemistry, University of Western Ontario, London, Ontario, Canada, N6A 5C1.
S D
SD
Dunn
L M
LM
Wahl
G B
GB
Gloor
D000465:Algorithms; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D019277:Entropy; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods*; D017421:Sequence Analysis / Q000379:methods*
D011506:Proteins