MISTIC: mutual information server to infer coevolution

Abstract

MISTIC (mutual information server to infer coevolution) is a web server for graphical representation of the information contained within a MSA (multiple sequence alignment) and a complete analysis tool for Mutual Information networks in protein families. The server outputs a graphical visualization of several information-related quantities using a circos representation. This provides an integrated view of the MSA in terms of (i) the mutual information (MI) between residue pairs, (ii) sequence conservation and (iii) the residue cumulative and proximity MI scores. Further, an interactive interface to explore and characterize the MI network is provided. Several tools are offered for selecting subsets of nodes from the network for visualization. Node coloring can be set to match different attributes, such as conservation, cumulative MI, proximity MI and secondary structure. Finally, a zip file containing all results can be downloaded. The server is available at http://mistic.leloir.org.ar. In summary, MISTIC allows for a comprehensive, compact, visually rich view of the information contained within an MSA in a manner unique to any other publicly available web server. In particular, the use of circos representation of MI networks and the visualization of the cumulative MI and proximity MI concepts is novel.

Experimental Analysis of Functional Variation within Protein Families: Receiver Domain Autodephosphorylation Kinetics

“…To examine coevolution of residues within receiver domains, in October 2015 we performed mutual information analysis of the Pfam Response_reg RP15 database (16) using the MISTIC server (http://mistic.leloir.org.ar/index.php) (17).…”

“…If two variable positions within a protein participate in a functionally important interaction, then the amino acids at the two positions would be expected to covary during evolution, as a change at one position leads to selection of a compensating change at the other position (17). When the mutual information content of all 5,995 possible pairwise comparisons within receiver domains was determined, most (10/13) of the pairs with Z-scores over 100 involved interactions that appeared to be important for protein structure.…”

A molecular modelling approach to understand the effect of co-evolutionary mutations (V344M, I354L) identified in the PB2 subunit of influenza A 2009 pandemic H1N1 virus on m7GTP ligand binding

“…The results from the server include the information of the multiple sequence alignment (MSA) condensed into a circos representation and a mutual information (MI) network, a distance network based on MI score if a reference protein structure is provided (Simonetti et al, 2013).…”

“…Continuous tracking of single and coevolutionary variations in the PB2 protein is thus vital in surveillance of the evolution and understanding of the pathogenic potential of the influenza virus. Further, co-evolutionary mutational positions gain significance if they are in close proximity, especially in the tertiary fold of the protein (Simonetti et al, 2013). Being associated with functional sites, the nature of residue co-evolution is such that it should maintain the overall functionality and structural integrity of the protein (Chakrabarti et al, 2010).…”

Can bioinformatics help in the identification of moonlighting proteins?

“…We have checked whether the MISTIC server [23] can help to predict moonlighting proteins. The main limitation of algorithms such as MISTIC is that they require a large multi-alignment; however, current families of moonlighting proteins are scarce, with enolases being the best example.…”