Folding of the 25 Residue Aβ(12−36) Peptide in TFE/Water:  Temperature-Dependent Transition from a Funneled Free-Energy Landscape to a Rugged One

Kamiya, Narutoshi; Mitomo, Daisuke; Shea, Joan–Emma; Higo, Junichi

doi:10.1021/jp067075v

Cited by 34 publications

(32 citation statements)

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“…The stabilization effect of fluorinated solvents has also been shown in other MD simulation studies of different peptides [95,[135][136][137] and proteins [138].…”

Section: Fluorinated Alcoholsmentioning

confidence: 54%

Computer Simulations Study of Biomolecules in Non-Aqueous or Cosolvent/Water Mixture Solutions

Roccatano

2008

CPPS

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Pure organic solvents or mixtures with water are very common environments for studying protein and peptide in solution. These milieu conditions are used either for improving the catalytic performance of enzymes or for studying the effect of solvent on the protein stability and hence gaining insight into the protein folding mechanism. The atomic details of these processes are mainly addressed using computer simulation approaches. In particular, Molecular Dynamics simulation represents the most powerful and versatile tool to investigate the details of solvation processes at atomic level. In the last few years, the number of publications peptide and protein simulations in non-natural environments has proliferated. These studies are providing important contributions to shed light on the nature of non-aqueous solvent effects. In this review, the achievements and the future prospects in this field of computational biochemistry are reviewed by summarizing the most important theoretical results published in the last 10 years.

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“…The stabilization effect of fluorinated solvents has also been shown in other MD simulation studies of different peptides [95,[135][136][137] and proteins [138].…”

Section: Fluorinated Alcoholsmentioning

confidence: 54%

Computer Simulations Study of Biomolecules in Non-Aqueous or Cosolvent/Water Mixture Solutions

Roccatano

2008

CPPS

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“…Typically, the folding free energy landscape of peptides shows the characteristic features of a funneled landscape, either with a downhill surface toward the folded basin or with a more rugged surface with local minima populating the unfolded basin 36,39–41 (a typical example is given in Figure 5). The degree of roughness was shown to strongly depend on the temperature 39–41. Comparison of the folding landscapes at different temperatures revealed that a temperature‐dependent transition from a funneled free energy landscape (at higher T) to a rugged one (at lower T) occurs for the studied peptides.…”

Section: Applicationsmentioning

confidence: 90%

Essential dynamics: foundation and applications

Daidone

Amadei

2012

WIREs Comput Mol Sci

117

119

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Collective coordinates, as obtained by a principal component analysis of atomic fluctuations, are commonly used to predict a low-dimensional subspace in which essential protein motion is expected to take place. The definition of such an essential subspace allows to characterize protein functional, and folding, motion, to provide insight into the (free) energy landscape, and to enhance conformational sampling in molecular dynamics simulations. Here, we provide an overview on the topic, giving particular attention to some methodological aspects, such as the problem of convergence, and mentioning possible new developments. (c) 2012 John Wiley & Sons, Ltd

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“…The McMD simulation of a 25-residue segment from the Alzheimer's β amyloid peptide (Aβ) in a TFE/water co-solvent showed that this peptide folds into the experimentally determined helical structure (Kamiya et al 2007), although it is disordered in water (Ikebe et al 2007a). The free-energy landscape was funnel-like above 325 K, where the funnel bottom corresponded to the experimental structure, and the landscape transitioned abruptly to a rugged one below 325 K. This work might have captured a general property of the temperature-induced structural transition exhibited by many peptides/proteins.…”

Section: All-atom Mcmd Simulations Of Various Systemsmentioning

confidence: 99%

Enhanced and effective conformational sampling of protein molecular systems for their free energy landscapes

et al. 2012

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Protein folding and protein–ligand docking have long persisted as important subjects in biophysics. Using multicanonical molecular dynamics (McMD) simulations with realistic expressions, i.e., all-atom protein models and an explicit solvent, free-energy landscapes have been computed for several systems, such as the folding of peptides/proteins composed of a few amino acids up to nearly 60 amino-acid residues, protein–ligand interactions, and coupled folding and binding of intrinsically disordered proteins. Recent progress in conformational sampling and its applications to biophysical systems are reviewed in this report, including descriptions of several outstanding studies. In addition, an algorithm and detailed procedures used for multicanonical sampling are presented along with the methodology of adaptive umbrella sampling. Both methods control the simulation so that low-probability regions along a reaction coordinate are sampled frequently. The reaction coordinate is the potential energy for multicanonical sampling and is a structural identifier for adaptive umbrella sampling. One might imagine that this probability control invariably enhances conformational transitions among distinct stable states, but this study examines the enhanced conformational sampling of a simple system and shows that reasonably well-controlled sampling slows the transitions. This slowing is induced by a rapid change of entropy along the reaction coordinate. We then provide a recipe to speed up the sampling by loosening the rapid change of entropy. Finally, we report all-atom McMD simulation results of various biophysical systems in an explicit solvent.

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Folding of the 25 Residue Aβ(12−36) Peptide in TFE/Water: Temperature-Dependent Transition from a Funneled Free-Energy Landscape to a Rugged One

Cited by 34 publications

References 50 publications

Computer Simulations Study of Biomolecules in Non-Aqueous or Cosolvent/Water Mixture Solutions

Computer Simulations Study of Biomolecules in Non-Aqueous or Cosolvent/Water Mixture Solutions

Essential dynamics: foundation and applications

Enhanced and effective conformational sampling of protein molecular systems for their free energy landscapes

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