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Handbook of Single-Molecule Biophysics pp 407–447Cite as

Probing the Energy Landscape of Protein-Binding Reactions by Dynamic Force Spectroscopy

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Abstract

This chapter describes how the energy landscape that underlies protein-binding reactions can be revealed using dynamic force spectroscopy. The chapter begins with a detailed description of methodologies used and requirements of the experimental system, including tip and surface materials and their functionalization strategies. The next few sections discuss the fundamentals of measuring forces using the atomic force microscope, and the basics of performing force spectroscopy measurements from a practical point of view. Next, it presents an extensive account of methods for data analysis and current theoretical treatments. The remainder of the chapter illustrates the power of this methodology by several examples in which the location of energy barriers in a binding reaction pathway and their load-dependent dynamics are measured, the overall scale of roughness of the underlying energy surface is extracted, and alternative modes of protein activation are distinguished. Biological insight gained from these data is discussed. The intent is to provide the necessary theoretical and practical knowledge to begin force spectroscopy measurements on protein interactions.

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Authors and Affiliations

  1. Institute for Biophysics, Johannes Kepler University of Linz, Altenbergerstr. 69, A-4040, Linz, Austria

    Andreas Ebner, Christian Ranki, Johannes Preiner, Hermann Gruber & Peter Hinterdorfer

  2. Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel, 76100

    Reinat Nevo, Ruti Kapon & Ziv Reich

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  1. Andreas Ebner
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  1. Institut für Biophysik, Universität Linz, Altenberger Straße 69, Linz, 4040, Austria

    Peter Hinterdorfer

  2. Harvard Medical School, Harvard University, Longwood Ave. 250, Boston, 02115, U.S.A.

    Antoine Oijen

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Ebner, A. et al. (2009). Probing the Energy Landscape of Protein-Binding Reactions by Dynamic Force Spectroscopy. In: Hinterdorfer, P., Oijen, A. (eds) Handbook of Single-Molecule Biophysics. Springer, New York, NY. https://doi.org/10.1007/978-0-387-76497-9_15

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