Functional analysis of enzyme families using residue-residue coevolution similarity networks

Residue-residue coevolution has been used to elucidate structural information of proteins. Networks of coevolution patterns have also been analysed to discover residues important for the function of individual enzymes. In this work, we take advantage of the functional importance of coevolving residues to perform network-based clustering of subsets of two enzyme families based on similarities of their coevolution patterns, or Coevolution Similarity Networks. The power of these networks in the functional analysis of sets of enzymes is explored in detail, using Sequence Similarity Networks as a benchmark to compare against.