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Evolutionary model of protein secondary structure capable of revealing new biological relationships
Author(s) -
Lai JhihSiang,
Rost Burkhard,
Kobe Bostjan,
Bodén Mikael
Publication year - 2020
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.25898
Subject(s) - phylogenetic tree , evolutionary biology , sequence (biology) , protein secondary structure , biology , phylogenetics , computational biology , protein structure prediction , inference , protein family , protein sequencing , protein structure , sequence alignment , multiple sequence alignment , peptide sequence , genetics , artificial intelligence , computer science , gene , biochemistry
Ancestral sequence reconstruction has had recent success in decoding the origins and the determinants of complex protein functions. However, phylogenetic analyses of remote homologues must handle extreme amino acid sequence diversity resulting from extended periods of evolutionary change. We exploited the wealth of protein structures to develop an evolutionary model based on protein secondary structure. The approach follows the differences between discrete secondary structure states observed in modern proteins and those hypothesized in their immediate ancestors. We implemented maximum likelihood‐based phylogenetic inference to reconstruct ancestral secondary structure. The predictive accuracy from the use of the evolutionary model surpasses that of comparative modeling and sequence‐based prediction; the reconstruction extracts information not available from modern structures or the ancestral sequences alone. Based on a phylogenetic analysis of a sequence‐diverse protein family, we showed that the model can highlight relationships that are evolutionarily rooted in structure and not evident in amino acid‐based analysis.