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Methods of Protein Structure Comparison

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Homology Modeling

Part of the book series: Methods in Molecular Biology ((MIMB,volume 857))

Abstract

Despite its apparent simplicity, the problem of quantifying the differences between two structures of the same protein or complex is nontrivial and continues evolving. In this chapter, we described several methods routinely used to compare computational models to experimental answers in several modeling assessments. The two major classes of measures, positional distance-based and contact-based, are presented, compared, and analyzed. The most popular measure of the first class, the global RMSD, is shown to be the least representative of the degree of structural similarity because it is dominated by the largest error. Several distance-dependent algorithms designed to attenuate the drawbacks of RMSD are described. Measures of the second class, contact-based, are shown to be more robust and relevant. We also illustrate the importance of using combined measures, utility-based measures, and the role of the distributions derived from the pairs of experimental structures in interpreting the results.

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Acknowledgments

Authors wish to thank the organizers and the participants of the GPCR Dock 2010 assessment for providing the model statistics, Max Totrov and Eugene Raush for implementing some of the core functions in ICM, Manuel Rueda for helpful discussions and Karie Wright for help with manuscript preparation. We would like to acknowledge financial support by NIH, grants # R01 GM071872, U01 GM094612, and U54 GM094618.

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Authors and Affiliations

  1. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA

    Irina Kufareva & Ruben Abagyan

  2. San Diego Supercomputer Center, University of California, San Diego, La Jolla, CA, USA

    Ruben Abagyan

Authors
  1. Irina Kufareva
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  2. Ruben Abagyan
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Corresponding author

Correspondence to Ruben Abagyan .

Editor information

Editors and Affiliations

  1. Molsoft L.L.C., Sorrento Valley Road 11199, S209 San Diego, 92121, California, USA

    Andrew J. W. Orry

  2. Skaggs School of Pharmacy &, Pharmaceutical Sciences, University of California, San Diego, Gilman Drive 9500, La Jolla, 92093, California, USA

    Ruben Abagyan

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Kufareva, I., Abagyan, R. (2011). Methods of Protein Structure Comparison. In: Orry, A., Abagyan, R. (eds) Homology Modeling. Methods in Molecular Biology, vol 857. Humana Press. https://doi.org/10.1007/978-1-61779-588-6_10

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  • DOI: https://doi.org/10.1007/978-1-61779-588-6_10

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-587-9

  • Online ISBN: 978-1-61779-588-6

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