Journal Article

Protein secondary structure appears to be robust under <i>in silico</i> evolution while protein disorder appears not to be

Christian Schaefer, Avner Schlessinger and Burkhard Rost

in Bioinformatics

Volume 26, issue 5, pages 625-631
Published in print March 2010 | ISSN: 1367-4803
Published online January 2010 | e-ISSN: 1460-2059 | DOI:

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Motivation: The mutation of amino acids often impacts protein function and structure. Mutations without negative effect sustain evolutionary pressure. We study a particular aspect of structural robustness with respect to mutations: regular protein secondary structure and natively unstructured (intrinsically disordered) regions. Is the formation of regular secondary structure an intrinsic feature of amino acid sequences, or is it a feature that is lost upon mutation and is maintained by evolution against the odds? Similarly, is disorder an intrinsic sequence feature or is it difficult to maintain? To tackle these questions, we in silico mutated native protein sequences into random sequence-like ensembles and monitored the change in predicted secondary structure and disorder.

Results: We established that by our coarse-grained measures for change, predictions and observations were similar, suggesting that our results were not biased by prediction mistakes. Changes in secondary structure and disorder predictions were linearly proportional to the change in sequence. Surprisingly, neither the content nor the length distribution for the predicted secondary structure changed substantially. Regions with long disorder behaved differently in that significantly fewer such regions were predicted after a few mutation steps. Our findings suggest that the formation of regular secondary structure is an intrinsic feature of random amino acid sequences, while the formation of long-disordered regions is not an intrinsic feature of proteins with disordered regions. Put differently, helices and strands appear to be maintained easily by evolution, whereas maintaining disordered regions appears difficult. Neutral mutations with respect to disorder are therefore very unlikely.


Supplementary Information: Supplementary data are available at Bioinformatics online.

Journal Article.  5464 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

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