Influence of conservation on calculations of amino acid covariance in multiple sequence alignments.
It has long been argued that algorithms that find correlated mutations in multiple sequence alignments can be used to find structurally or functionally important residues in proteins. We examined the properties of four different methods for detecting these correlated mutations. On both simple, artificial alignments and real alignments from the Pfam database, we found a surprising lack of agreement between the four correlated mutation methods. We argue that these differences are caused in part by differing sensitivities to background conservation. Correlated mutation algorithms can be envisioned as "filters" of background conservation with each algorithm searching for correlated mutations that occur at a different background conservation frequency.
Fodor
Anthony A
AA
Department of Molecular and Cellular Physiology, and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5345, USA.
Aldrich
Richard W
RW
D000465:Algorithms; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D030562:Databases, Protein; D009154:Mutation; D011336:Probability; D011487:Protein Conformation; D016415:Sequence Alignment
D000596:Amino Acids