ProPhylER: A Curated Online Resource for Protein Function and Structure Based on Evolutionary Constraint Analyses

Abstract

ProPhylER (Protein Phylogeny and Evolutionary Rates) is a next-generation curated proteome resource that uses comparative sequence analysis to predict constraint and mutation impact for eukaryotic proteins. Its purpose is to inform any research program for which protein function and structure is relevant, by the predictive power of evolutionary constraint analyses. ProPhylER currently has nearly 9,000 clusters of related proteins, including more than 200,000 sequences. It serves data via two interfaces. The ProPhylER Interface displays predictive analyses in sequence space; the CrystalPainter maps evolutionary constraints onto solved protein structures. Here we summarize ProPhylERs data content and analysis pipeline, demonstrate the use of ProPhylERs interfaces, and evaluate ProPhylERs unique regional analysis of evolutionary constraint. The high accuracy of ProPhylERs regional analysis complements the high resolution of its single-site analysis to effectively guide and inform structure-function investigations and predict the impact of polymorphisms. ProPhylERs interfaces, analyses and data can be accessed at www.prophyler.org.