Small protein fragments, and not just residues, can be used as basic building blocks to reconstruct networks of coevolved amino acids in proteins. Fragments often enter in physical contact one with the other and play a major biological role in the protein. The nature of these interactions might be multiple and spans beyond binding specificity, allosteric regulation and folding constraints. Indeed, coevolving fragments are indicators of important information explaining folding intermediates, peptide assembly, key mutations with known roles in genetic diseases, distinguished subfamily-dependent motifs and differentiated evolutionary pressures on protein regions. BIS coevolution analysis detects networks of fragments interaction and highlights a high order organization of fragments demonstrating the importance of studying at a deeper level this structure. BIS can be applied to protein families that are highly conserved or represented by few sequences, enlarging in this manner, the class of proteins where coevolution analysis can be performed and making large-scale coevolution studies a feasible goal.
The BIS package is available here.
Linux or Mac OS X.
The program BIS uses several external tools that should be installed:
BIS also uses the clustering program CLAG (that clusterizes
matrices of coevolution scores; downloadable at
http://www.ihes.fr/carbone/data11) that we include in the package
and needs not be installed. For an independent CLAG usage, see CLAG R package,
especially designed to make CLAG use simple.
The instructions for running BIS and reading its output files are here. BIS can be run in different modes:
Also, fragment analysis can be realized on positions with (at most) d exceptions (parameter "-d=1" for instance, when 1 exception is tolerated) or in all positions (option "-a=y").
Example of a BIS fragment analysis:
./exe.pl -f=put-correct-path/452 -d=0 -h=y -e=put-correct-path/TOOLBIS -s=put-correct-path/Setup -o=linuxReplace "put-correct-path" by the correct paths and "linux" by macOSX depending on your OS (it must be the exact suffix to the PhyML executable)
./exe-RCommand.pl -f=put-correct-path/452 -d=0 -e=put-correct-path/TOOLBISThis will take only a few seconds.
Things to be careful about:
For questions, comments or suggestions feel free to contact Alessandra Carbone or Linda Dib.
Last Update May 2013