About Evolutionary Trace

The structure and function of proteins underlie most aspects of biology and their mutational perturbations often cause disease. A central question is which protein residue positions are important and cluster to form functional sites.

As a solution to this question, the Evolutionary Trace (ET) computes the relative rank of functional and structural importance among protein homologs sequence positions. The rank is lower if sequence positions vary among evolutionarily closer homologs and higher if the positions vary among evolutionarily distant homologs. Thus, ET uses evolutionary distances as a proxy for functional distances to correlate genotype variations with phenotype, or fitness, variations. This approach identifies functional determinants, predicts function, guides the mutational redesign of functional and allosteric specificity, and interprets the action of coding sequence variations in proteins, people, and populations.