COVTree: Coevolution in OVerlapped sequences by Tree analysis server.

Overlapping genes are commonplace in viruses and play an important role in their function and evolution. For these genes, molecular coevolution may be seen as a mechanism to decrease the evolutionary constraints of amino acid positions in the overlapping regions and to tolerate or compensate unfavorable mutations. Tracing these mutational sites, could help to gain insight on the direct or indirect effect of the mutations in the corresponding overlapping proteins. In the past, coevolution analysis has been used to identify residue pairs and coevolutionary signatures within or between proteins that served as markers of physical interactions and/or functional relationships. Coevolution in OVerlapped sequences by Tree analysis (COVTree) is a web server providing the online analysis of coevolving amino-acid pairs in overlapping genes, where residues might be located inside or outside the overlapping region. COVTree is designed to handle protein families with various characteristics, among which those that typically display a small number of highly conserved sequences. It is based on BIS2, a fast version of the coevolution analysis tool Blocks in Sequences (BIS). COVTree provides a rich and interactive graphical interface to ease biological interpretation of the results and it is openly accessible at http://www.lcqb.upmc.fr/COVTree/.

MIToS.jl: mutual information tools for protein sequence analysis in the Julia language.

Motivation: MIToS is an environment for mutual information analysis and a framework for protein multiple sequence alignments (MSAs) and protein structures (PDB) management in Julia language. It integrates sequence and structural information through SIFTS, making Pfam MSAs analysis straightforward. MIToS streamlines the implementation of any measure calculated from residue contingency tables and its optimization and testing in terms of protein contact prediction. As an example, we implemented and tested a BLOSUM62-based pseudo-count strategy in mutual information analysis. Availability and Implementation: The software is totally implemented in Julia and supported for Linux, OS X and Windows. It's freely available on GitHub under MIT license: http://mitos.leloir.org.ar . Contacts: diegozea@gmail.com or cmb@leloir.org.ar. Supplementary information: Supplementary data are available at Bioinformatics online.

I-COMS: Interprotein-COrrelated Mutations Server.

Interprotein contact prediction using multiple sequence alignments (MSAs) is a useful approach to help detect protein-protein interfaces. Different computational methods have been developed in recent years as an approximation to solve this problem. However, as there are discrepancies in the results provided by them, there is still no consensus on which is the best performing methodology. To address this problem, I-COMS (interprotein COrrelated Mutations Server) is presented. I-COMS allows to estimate covariation between residues of different proteins by four different covariation methods. It provides a graphical and interactive output that helps compare results obtained using different methods. I-COMS automatically builds the required MSA for the calculation and produces a rich visualization of either intraprotein and/or interprotein covariating positions in a circos representation. Furthermore, comparison between any two methods is available as well as the overlap between any or all four methodologies. In addition, as a complementary source of information, a matrix visualization of the corresponding scores is made available and the density plot distribution of the inter, intra and inter+intra scores are calculated. Finally, all the results can be downloaded (including MSAs, scores and graphics) for comparison and visualization and/or for further analysis.

Intrinsically Disordered Protein Ensembles Shape Evolutionary Rates Revealing Conformational Patterns.

Intrinsically disordered proteins (IDPs) lack stable tertiary structure under physiological conditions. The unique composition and complex dynamical behaviour of IDPs make them a challenge for structural biology and molecular evolution studies. Using NMR ensembles, we found that IDPs evolve under a strong site-specific evolutionary rate heterogeneity, mainly originated by different constraints derived from their inter-residue contacts. Evolutionary rate profiles correlate with the experimentally observed conformational diversity of the protein, allowing the description of different conformational patterns possibly related to their structure-function relationships. The correlation between evolutionary rates and contact information improves when structural information is taken not from any individual conformer or the whole ensemble, but from combining a limited number of conformers. Our results suggest that residue contacts in disordered regions constrain evolutionary rates to conserve the dynamic behaviour of the ensemble and that evolutionary rates can be used as a proxy for the conformational diversity of IDPs.