Mapping the Mutual Information Network of Enzymatic Families in the Protein Structure to Unveil Functional Features

AGUILAR DANIEL; OLIVA BALDO; CRISTINA MARINO BUSLJE

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2012 vol. 7 p. 1 - 8

1932-6203

Amino acids committed to a particular function correlate tightly along evolution and tend to form clusters in the 3Dstructure of the protein. Consequently, a protein can be seen as a network of co-evolving clusters of residues. The goal ofthis work is two-fold: first, we have combined mutual information and structural data to describe the amino acid networkswithin a protein and their interactions. Second, we have investigated how this information can be used to improve methodsof prediction of functional residues by reducing the search space. As a main result, we found that clusters of co-evolvingresidues related to the catalytic site of an enzyme have distinguishable topological properties in the network. We alsoobserved that these clusters usually evolve independently, which could be related to a fail-safe mechanism. Finally, wediscovered a significant enrichment of functional residues (e.g. metal binding, susceptibility to detrimental mutations) in theclusters, which could be the foundation of new prediction tools.