Predicting co-evolving pairs in Pfam using information theory where entropy is determined by phylogenetic mutation events

The accurate prediction of co-evolving pairs in protein sequences plays an important role in tertiary protein structure prediction and protein engineering. Using information theory to detect co-evolving pairs is impacted by the phylogenetic effect on entropy measurements. Mutual Information (MI) is used to detect co-evolving pairs in a protein family by re-sampling based on mutation events in the phylogenetic tree (RPE).