Network Analysis of Protein Adaptation: modeling the functional impact of multiple mutations

April 17, 2018

NCBI Article Fig1

The article, Network Analysis of Protein Adaptation: modeling the functional impact of multiple mutations, analyzes co-dependencies between mutations in clusters of proteins undergoing recent evolutionary radiation as they evolve under new selective pressures. This is a radical departure from an analysis of function-preserving mutation dependencies, which is based on comparing sequences that have drifted over long evolutionary periord.  As proof of principle, Karchin and Camps analyzed three protein clusters that are distinct both in sequence and in selective pressure. They find that  co-dependencies typically involve residues distal in protein structure. Based on the topology of the co-evolutionary networks, they were able to identify key adaptive mutations, predict positive pairwise interactions, and anticipate complex evolutionary trajectories likely to increase resistance. Importantly, this work did not require any prior structural or biochemical information and should therefore be of great use as databases of mutations outpace our ability to characterize mutants.