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Estimation of Folding Probabilities and Φ Values From Molecular Dynamics Simulations of Reversible Peptide Folding

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Protein Folding Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 350))

Abstract

Molecular dynamics simulations with an implicit model of the solvent have allowed to investigate the reversible folding of structured peptides.

For a 20-residue antiparallel β-sheet peptide, the simulation results have revealed multiple folding pathways. Moreover, the conformational heterogeneity of the denatured state has been shown to originate from high enthalpy, high entropy basins with fluctuating non-native secondary structure, as well as low enthalpy, low entropy traps. An efficient and simple approach to estimate folding probabilities from molecular dynamics simulations has allowed to isolate conformations in the transition state ensemble and to evaluate Φ values, i.e., the effects of mutations on the folding kinetics and thermodynamic stability. These molecular dynamics studies have provided evidence that, if interpreted by neglecting the non-native interactions, Φ values overestimate the amount of native-like structure in the transition state.

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Notes

  1. 1.

    *

    In contrast with the astronomical amount of time needed by a random search in the configuration space of the protein (Levinthal’s paradox).

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Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Zürich, Zürich, Switzerland

    Francesco Rao, Giovanni Settanni & Amedeo Caflisch

Authors
  1. Francesco Rao
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  2. Giovanni Settanni
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  3. Amedeo Caflisch
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Editor information

Editors and Affiliations

  1. Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD

    Yawen Bai

  2. Center for Cancer Research Nanobiology Program SAIC, National Cancer Institute-Frederick, Frederick, MD

    Ruth Nussinov

  3. Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Ruth Nussinov

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© 2007 Humana Press Inc.

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Rao, F., Settanni, G., Caflisch, A. (2007). Estimation of Folding Probabilities and Φ Values From Molecular Dynamics Simulations of Reversible Peptide Folding. In: Bai, Y., Nussinov, R. (eds) Protein Folding Protocols. Methods in Molecular Biology™, vol 350. Humana Press. https://doi.org/10.1385/1-59745-189-4:225

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  • DOI: https://doi.org/10.1385/1-59745-189-4:225

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-622-1

  • Online ISBN: 978-1-59745-189-5

  • eBook Packages: Springer Protocols

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