Using information theory to search for co-evolving residues in proteins.
BACKGROUND
Some functionally important protein residues are easily detected since they correspond to conserved columns in a multiple sequence alignment (MSA). However important residues may also mutate, with compensatory mutations occurring elsewhere in the protein, which serve to preserve or restore functionality. It is difficult to distinguish these co-evolving sites from other non-conserved sites.


RESULTS
We used Mutual Information (MI) to identify co-evolving positions. Using in silico evolved MSAs, we examined the effects of the number of sequences, the size of amino acid alphabet and the mutation rate on two sources of background MI: finite sample size effects and phylogenetic influence. We then assessed the performance of various normalizations of MI in enhancing detection of co-evolving positions and found that normalization by the pair entropy was optimal. Real protein alignments were analyzed and co-evolving isolated pairs were often found to be in contact with each other.


BACKGROUND
All data and program files can be found at http://www.biochem.uwo.ca/cgi-bin/CDD/index.cgi
Martin
L C
LC
Department of Applied Mathematics, University of Western Ontario, London, Canada.
Gloor
G B
GB
Dunn
S D
SD
Wahl
L M
LM
D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D030541:Databases, Genetic; D030562:Databases, Protein; D019143:Evolution, Molecular; D008040:Genetic Linkage; D007257:Information Theory; D015233:Models, Statistical; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D012680:Sensitivity and Specificity; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D014305:Triose-Phosphate Isomerase / Q000737:chemistry
D011506:Proteins; D014305:Triose-Phosphate Isomerase