Signals of Evolution: Conservation, Specificity Determining Positions and Coevolution

ELIN TEPPA; DIEGO ZEA; MORTEN NIELSEN; CRISTINA MARINO BUSLJE

Córdoba

Congreso; 2do Congreso Argentino de Bioinformática y Biología Computacional (CAB2C); 2011

Asociación Argentina de Bioinformática y Biología Computacional

Protein sequences evolve under several constraints and every each constraint leads to a specific pattern of conservation and variation in protein sequences. In this study we focused on the analysis of three major evolutionary signals: conservation, specificity determining positions and coevolution between residues. These signals are results of different evolutionary mechanisms and have been used by different bioinformatics methods to predict functionally important sites. Fully conserved position in a Multiple Sequence Alignment (MSA) are interpreted as important residues for the structure and function of the protein. At the beginning, the computational methods used this information to predict functional important sites including catalytic residues. Nowadays, more factors are taken into account to improve the performance of prediction methods. Other positions show a more subtle pattern of conservation, they are conserved within a group of sequences (sub-family) but may change in another group. Such positions are responsible for protein specificity i.e. ligand binding, protein-protein interaction, etc. (named: Specificity-Determining Positions –SDPs- ). The classification of proteins into groups can be defined according to different criteria i.e. identity, phylogenetically, functional similarity, among others. SDPs are suggested to be located in the proximity of the catalytic residues in order to carry out their role of defining the substrate specificity. Coevolution between residues is another signal that can be extracted from MSAs. Coevolution is the result of compensatory mutations, namely they are those residues that have undergone concerted changes to overcome a common selection pressure. Owing to the limitations on the amino acid diversity in the proximity of an active site, the catalytic residues carry a particular signature defined by a close proximity network of residues with high mutual information. In summary, in this study we consider different methods that attempt to capture information from three different evolutionary signals. They have in common the prediction of functionally important sites and are capable of detecting the catalytic residues by itself or to point the residues nearby the catalytic residues. Disentangling the function of different positions in an alignment will allows us to create methods that take profit from different information contained in an alignment. That could be use for the deeper study of any proteins. Besides it would help to do better and accurate annotations of proteins with unknown function.