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Predicting evolutionary site variability from structure in viral proteins: buriedness, packing, flexibility, and design

Amir Shahmoradi, Dariya K. Sydykova, Stephanie J. Spielman, Eleisha L. Jackson, Eric T. Dawson, Austin G. Meyer, Claus O. Wilke
doi: https://doi.org/10.1101/004481
Amir Shahmoradi
1Department of Physics, The University of Texas at Austin, TX, 78712.
2Department of Integrative Biology, Center for Computational Biology and Bioinformatics, and Institute for Cellular and Molecular Biology, The University of Texas at Austin, TX, 78712. E-mail:
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  • For correspondence: wilke@austin.utexas.edu
Dariya K. Sydykova
2Department of Integrative Biology, Center for Computational Biology and Bioinformatics, and Institute for Cellular and Molecular Biology, The University of Texas at Austin, TX, 78712. E-mail:
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  • For correspondence: wilke@austin.utexas.edu
Stephanie J. Spielman
2Department of Integrative Biology, Center for Computational Biology and Bioinformatics, and Institute for Cellular and Molecular Biology, The University of Texas at Austin, TX, 78712. E-mail:
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  • For correspondence: wilke@austin.utexas.edu
Eleisha L. Jackson
2Department of Integrative Biology, Center for Computational Biology and Bioinformatics, and Institute for Cellular and Molecular Biology, The University of Texas at Austin, TX, 78712. E-mail:
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Eric T. Dawson
2Department of Integrative Biology, Center for Computational Biology and Bioinformatics, and Institute for Cellular and Molecular Biology, The University of Texas at Austin, TX, 78712. E-mail:
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  • For correspondence: wilke@austin.utexas.edu
Austin G. Meyer
2Department of Integrative Biology, Center for Computational Biology and Bioinformatics, and Institute for Cellular and Molecular Biology, The University of Texas at Austin, TX, 78712. E-mail:
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Claus O. Wilke
2Department of Integrative Biology, Center for Computational Biology and Bioinformatics, and Institute for Cellular and Molecular Biology, The University of Texas at Austin, TX, 78712. E-mail:
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  • For correspondence: wilke@austin.utexas.edu
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Abstract

Several recent works have shown that protein structure can predict site-specific evolutionary sequence variation. In particular, sites that are buried and/or have many contacts with other sites in a structure have been shown to evolve more slowly, on average, than surface sites with few contacts. Here, we present a comprehensive study of the extent to which numerous structural properties can predict sequence variation. The quantities we considered include buriedness (as measured by relative solvent accessibility), packing density (as measured by contact number), structural flexibility (as measured by B factors, root-mean-square fluctuations, and variation in dihedral angles), and variability in designed structures. We obtained structural flexibility measures both from molecular dynamics simulations performed on 9 non-homologous viral protein structures and from variation in homologous variants of those proteins, where available. We obtained measures of variability in designed structures from flexible-backbone design in the Rosetta software. We found that most of the structural properties correlate with site variation in the majority of structures, though the correlations are generally weak (correlation coefficients of 0.1 to 0.4). Moreover, we found that buriedness and packing density were better predictors of evolutionary variation than was structural flexibility. Finally, variability in designed structures was a weaker predictor of evolutionary variability than was buriedness or packing density, but it was comparable in its predictive power to the best structural flexibility measures. We conclude that simple measures of buriedness and packing density are better predictors of evolutionary variation than are more complicated predictors obtained from dynamic simulations, ensembles of homologous structures, or computational protein design.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 21, 2014.
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Predicting evolutionary site variability from structure in viral proteins: buriedness, packing, flexibility, and design
Amir Shahmoradi, Dariya K. Sydykova, Stephanie J. Spielman, Eleisha L. Jackson, Eric T. Dawson, Austin G. Meyer, Claus O. Wilke
bioRxiv 004481; doi: https://doi.org/10.1101/004481
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Predicting evolutionary site variability from structure in viral proteins: buriedness, packing, flexibility, and design
Amir Shahmoradi, Dariya K. Sydykova, Stephanie J. Spielman, Eleisha L. Jackson, Eric T. Dawson, Austin G. Meyer, Claus O. Wilke
bioRxiv 004481; doi: https://doi.org/10.1101/004481

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