Use of mutual information theory to investigate the folding of a protein. Thioredoxin family of proteins as a model system.

MARINO-BUSLJE, C; SANTOS, J; NIELSEN, M; DELFINO, J M

Montevideo, Uruguay

Congreso; 6th International Conference on Biological Physics and the 5th Southern Cone Biophysics Congress; 2007

Use of mutual information theory to investigate the folding of a protein. Thioredoxin family of proteins as a model system. Cristina Marino Buslje, Javier Santos, Morten Nielsen y Jose Maria Delfino. Binding of the C-terminal helix to the rest of the protein in E. coli thioredoxin (trx) may signify a late event in the consolidation of the global structure of the protein, as was recently demonstrated by Santos et al. (2007). This recognition event across the trx family will be investigated through the mutual information (MI) theory. [ref]. We have found that an identical helix is present in two other protein families endowed with different folds and functions. By means of applying this computational technique we intend to detect “folding blocks”, i. e. those residues in the opposing surface that interact with the helix. Furthermore any pair of residues with mutual information will be investigated across the whole trx family (~3200 sequences  according to Pfam-) As we found shortcomings in the available software (e.g. gap treatment, background of the results, “bias” for sequence number, etc) we developed a program at home by following the specifications that we consider of interest to carry out this experiment and to render it more universally applicable. In the course we will run independent sets of proteins to measure the performance of the software and in so doing its generality. By filtering residues by their exposed surface, we will evaluate if we are able to detect mutual information due to (i) a folding requirement, (ii) direct interaction (if the residues are at a distance less than 10 Å), or (iii) by interacting through an intervening structure ( if the distance is more than 10 Å).