Predincting protein function from sequence and structural data: a globin's family case

BUSTAMANTE, JUAN PABLO; ARJEN TEN HAVE; MARTÍ, MARCELO ADRIÁN; ESTRIN, DARÍO

Congreso; 3er Congreso Argentino de Bioinformática y Biología Computacional; 2012

Predicting function from sequence and/or structure are key issues in bioinformatics. Although a broad functional assignment can be done by assigning a protein to a given family (or domain), determining a protein particular function is not straightforward. Assuming that the function is coded in the structure through the determination of its chemical properties, it is possible in principle to predict a putative function if relevant properties can be computed. The globins family of heme proteins offer a large, diverse and thoroughly studied set of proteins, whose function is tightly related to small ligand (mainly O2 but also NO, CO, and H2S) affinity and reactivity with the active site heme. Globins with high oxygen affinity usually function as O2-redox related enzymes, moderate affinity globins usually act as oxygen carriers, while low O2 affinity globins are NO or CO sensors. Ligand affinity is determined by the ratio between association (kon) and dissociation rate (koff). The first one is mainly related with the ligand migration process from the solvent to the protein active site, which is determined by the presence of internal tunnels and cavities and residues acting as “gates”, while the second is determined by interactions between protein and bound ligand. During the last decade our group has developed several in-silico methods to determine both processes based solely on structural information, showing excellent agreement with the experimental data for several particular cases. This fact prompted us to extend our analysis to a whole family of proteins, in this case the truncated hemoglobins (trHbs). TrHbs are a distinct widespread phylogenetic group of the globins family, which is divided in three different groups: I, II and III (also labeled N, O and P), for which about 350 different sequences have been reported, and existing at least one determined structure for each subgroup.