Estimation of folding probabilities and Phi values from molecular dynamics simulations of reversible peptide folding

TitleEstimation of folding probabilities and Phi values from molecular dynamics simulations of reversible peptide folding
Publication TypeBook Chapter
Year of Publication2007
AuthorsRao F., Settanni G., Caflisch A.
EditorBai Y., Nussinov R.
Book TitleProtein Folding Protocols
Series TitleMethods in Molecular Biology
Chapter13
Series Volume350
Pagination225-249
PublisherHumana Press, Inc.
CityTotowa, NJ
ISBN Number978-1-58829-622-1
Keywordsdenatured state ensemble, energy landscape, implicit solvent molecular dynamics, Protein Folding, transition state ensemble
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.

DOI10.1385/1-59745-189-4:225
pubindex

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