![]() ![]() ![]() Co-evolved residues have been demonstrated, for a few protein complexes (for which experimental data are available), to play a crucial role in allosteric mechanisms ( 1, 3, 10), to maintain short paths in network communication and to mediate signaling ( 11, 12). All these methods provide sets of co-evolved residues that are usually physically close in the 3D structure ( 1– 9) and form connected networks covering roughly a third of the entire structure. Several studies addressed the problem of extracting signals of co-evolution between residues. Co-evolving residues in a protein structure, possibly a complex, correspond to groups of residues whose mutations have arisen simultaneously during the evolution of different species and this is due to several possible reasons involving the 3D shape of the protein: functional interactions, conformational changes and folding. In recent years, a particular focus has been drawn to the study of co-evolving residues within a protein and among proteins. BIS2Analyzer provides a rich and interactive graphical interface to ease biological interpretation of the results. It is based on BIS 2, a re-implemented fast version of the co-evolution analysis tool Blocks in Sequences (BIS). BIS2Analyzer, openly accessible at, is a web server providing the online analysis of co-evolving amino-acid pairs in protein alignments, especially designed for vertebrate and viral protein families, which typically display a small number of highly similar sequences. Depending on the type of protein under study, the set of available homologous sequences may greatly differ in size and amino acid variability. In both cases, independently of the underlying cause, co-evolutionary signatures within or between proteins serve as markers of physical interactions and/or functional relationships. Along protein sequences, co-evolution analysis identifies residue pairs demonstrating either a specific co-adaptation, where changes in one of the residues are compensated by changes in the other during evolution or a less specific external force that affects the evolutionary rates of both residues in a similar magnitude. ![]()
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