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Protein Folding in Vivo: From Anfinsen Back to Levinthal

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Nonlinear Systems, Vol. 2

Part of the book series: Understanding Complex Systems ((UCS))

Abstract

In this chapter two visions of the protein folding process are confronted. The first is based on the thermodynamic hypothesis and the second is based on the kinetic hypothesis. Experimental results in support of each of the theories are reviewed and in some cases re-interpreted. While the thermodynamic hypothesis has been dominant since the 1970s, here it is argued that the experimental evidence favours the kinetic hypothesis, particularly in what concerns folding in vivo. A specific kinetic process, designated as the VES KM, is proposed. According to the VES KM the structure that all proteins have as they emerge from the ribosome is helical and the first step in folding is the bending of this helix at specific amino acid sites (i.e. the location of the bending sites depends on the protein sequence). Results from molecular dynamics simulations on a small all-\(\alpha \) protein demonstrate the theoretical viability of the VES KM. The chapter ends with a discussion on the state of the art in protein folding from the point of view of the VES KM and with proposals for future work.

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Acknowledgements

L.C. received national funds from FCT - Foundation for Science and Technology, Portugal, through the project UID/Multi/04326/2013. The author also acknowledges the Laboratory for Advanced Computing at University of Coimbra (http://www.lca.uc.pt) for providing HPC computing resources that have contributed to the research results reported within this paper.

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  1. Centro de Ciências do Mar and Faculdade de Ciências e Tecnologia, Universidade do Algarve, Campus de Gambelas, 8005-139, Faro, Portugal

    Leonor Cruzeiro

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  1. Departamento de Fisica Aplicada I, ETSI Informática, Universidad de Sevilla, Sevilla, Spain

    Juan F. R. Archilla

  2. Departamento de Fisica Aplicada I, ETSI Informática, Universidad de Sevilla, Sevilla, Spain

    Faustino Palmero

  3. Departamento de Física de la Materia Condensada, Universidad de Sevilla, Sevilla, Spain

    M. Carmen Lemos

  4. Departamento de Fisica Aplicada I, EPS, Universidad de Sevilla, Sevilla, Spain

    Bernardo Sánchez-Rey

  5. Departamento de Física Atómica, Molecular y Nuclear, Universidad de Sevilla, Sevilla, Spain

    Jesús Casado-Pascual

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Cruzeiro, L. (2018). Protein Folding in Vivo: From Anfinsen Back to Levinthal. In: Archilla, J., Palmero, F., Lemos, M., Sánchez-Rey, B., Casado-Pascual, J. (eds) Nonlinear Systems, Vol. 2. Understanding Complex Systems. Springer, Cham. https://doi.org/10.1007/978-3-319-72218-4_1

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