Predicting Protein Functional Sites with Phylogenetic Motifs: Past, Present and Beyond

Abstract

More than sequence or structure, function imposes very tight constraints on the evolutionary variability within a protein family. As such, numerous functional site prediction methods are based on algorithms to uncover conserved regions that lead to conserved function. Nevertheless, evolution does allow for some systematic variability within functional regions. Based on this tenet, we have introduced the MINER algorithm to predict functional regions from phylogenetic motifs. Specifically, our approach identifies alignment fragments that parallel the overall phylogeny of the family, which are more likely to be functional due to increased evolutionary signature. In this chapter, we provide an overview of the method, summarize recent developments, and comment on future work.