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Easy Not Easy: Comparative Modeling with High-Sequence Identity Templates

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Homology Modeling

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2627))

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Abstract

Homology modeling is the most common technique to build structural models of a target protein based on the structure of proteins with high-sequence identity and available high-resolution structures. This technique is based on the idea that protein structure shows fewer changes than sequence through evolution. While in this scenario single mutations would minimally perturb the structure, experimental evidence shows otherwise: proteins with high conformational diversity impose a limit of the paradigm of comparative modeling as the same protein sequence can adopt dissimilar three-dimensional structures. These cases present challenges for modeling; at first glance, they may seem to be easy cases, but they have a complexity that is not evident at the sequence level. In this chapter, we address the following questions: Why should we care about conformational diversity? How to consider conformational diversity when doing template-based modeling in a practical way?

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Author information

Author notes

  1. Diego Javier Zea and Elin Teppa contributed equally with all other contributors.

Authors and Affiliations

  1. Laboratory of Computational and Quantitative Biology, LCQB, UMR 7238 CNRS, IBPS, Sorbonne Université, Paris, France

    Diego Javier Zea

  2. Toulouse Biotechnology Institute, TBI, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France

    Elin Teppa

  3. Fundacion Instituto Leloir, Buenos Aires, Argentina

    Cristina Marino-Buslje

Authors
  1. Diego Javier Zea
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  2. Elin Teppa
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  3. Cristina Marino-Buslje
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Corresponding author

Correspondence to Cristina Marino-Buslje .

Editor information

Editors and Affiliations

  1. Faculty of Chemistry, University of Warsaw, Warsaw, Poland

    Sławomir Filipek

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Zea, D.J., Teppa, E., Marino-Buslje, C. (2023). Easy Not Easy: Comparative Modeling with High-Sequence Identity Templates. In: Filipek, S. (eds) Homology Modeling. Methods in Molecular Biology, vol 2627. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2974-1_5

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  • DOI: https://doi.org/10.1007/978-1-0716-2974-1_5

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2973-4

  • Online ISBN: 978-1-0716-2974-1

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