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Symmetric Protein Architecture in Protein Design: Top-Down Symmetric Deconstruction

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Book cover Protein Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1216))

Abstract

Top-down symmetric deconstruction (TDSD) is a joint experimental and computational approach to generate a highly stable, functionally benign protein scaffold for intended application in subsequent functional design studies. By focusing on symmetric protein folds, TDSD can leverage the dramatic reduction in sequence space achieved by applying a primary structure symmetric constraint to the design process. Fundamentally, TDSD is an iterative symmetrization process, in which the goal is to maintain or improve properties of thermodynamic stability and folding cooperativity inherent to a starting sequence (the “proxy”). As such, TDSD does not attempt to solve the inverse protein folding problem directly, which is computationally intractable. The present chapter will take the reader through all of the primary steps of TDSD—selecting a proxy, identifying potential mutations, establishing a stability/folding cooperativity screen—relying heavily on a successful TDSD solution for the common β-trefoil fold.

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Authors and Affiliations

  1. Department of Biomedical Sciences, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, FL, 32306-4300, USA

    Liam M. Longo & Michael Blaber

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  1. Liam M. Longo
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  2. Michael Blaber
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Correspondence to Michael Blaber .

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Editors and Affiliations

  1. Department of Chemistry, University of Basel, Switzerland

    Valentin Köhler

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Longo, L.M., Blaber, M. (2014). Symmetric Protein Architecture in Protein Design: Top-Down Symmetric Deconstruction. In: Köhler, V. (eds) Protein Design. Methods in Molecular Biology, vol 1216. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1486-9_8

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  • DOI: https://doi.org/10.1007/978-1-4939-1486-9_8

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1485-2

  • Online ISBN: 978-1-4939-1486-9

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