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Comparing Models of Evolution for Ordered and Disordered Proteins
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BibTeX
@MISC{Brown_comparingmodels,
author = {Celeste J. Brown and Audra K. Johnson and Gary W. Daughdrill},
title = {Comparing Models of Evolution for Ordered and Disordered Proteins},
year = {}
}
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Abstract
Most models of protein evolution are based upon proteins that form relatively rigid 3D structures. A significant fraction of proteins, the so-called disordered proteins, do not form rigid 3D structures and sample a broad conformational ensemble. Disordered proteins do not typically maintain long-range interactions, so the constraints on their evolution should be different than ordered proteins. To test this hypothesis, we developed and compared models of evolution for disordered and ordered proteins. Substitution matrices were constructed using the sequences of putative homologs for sets of experimentally characterized disordered and ordered proteins. Separate matrices, at three levels of sequence similarity (.85%, 85–60%, and 60–40%), were inferred for each type of protein structure. The substitution matrices for disordered and ordered proteins differed significantly at each level of sequence similarity. The disordered matrices reflected a greater likelihood of evolutionary changes, relative to the ordered matrices, and these changes involved nonconservative substitutions. Glutamic acid and asparagine were interesting exceptions to this result. Important differences between the substitutions that are accepted in disordered proteins relative to ordered proteins were also identified. In general, disordered proteins have fewer evolutionary constraints than ordered proteins. However, some residues like tryptophan and tyrosine are highly conserved in disordered proteins. This is due to their important role in forming protein–protein interfaces. Finally, the amino acid frequencies for disordered proteins, computed during the development of the matrices,
Keyphrases
disordered protein ordered protein substitution matrix sequence similarity important role amino acid frequency broad conformational ensemble nonconservative substitution disordered matrix long-range interaction protein structure ordered matrix separate matrix evolutionary change protein evolution interesting exception glutamic acid putative homologs evolutionary constraint important difference so-called disordered protein significant fraction protein protein interface
