Protein folding in a reverse micelle environment: The role of confinement and dehydration

Martinez, Anna Victoria; Domı́nguez, Laura; Rivera, Eva; Straub, John E.

doi:10.1063/1.3545982

Cited by 27 publications

(25 citation statements)

References 62 publications

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“…19 Our previous computational studies of RM confined peptides followed earlier work by Mukherjee et al 17,18 in which the secondary structure stability of monomers of the 19-residue, alanine-rich AKA 2 peptide in spherically restrained and unrestrained AOT RMs and in bulk water was analyzed. 34 In agreement with experiment, these studies showed increased helical content for peptides in RMs as compared to bulk water. They also revealed that the shape of the simulated RMs fluctuated significantly allowing the peptides to interact with the AOT surfactant molecules in addition to the core water molecules.…”

Section: Introductionsupporting

confidence: 75%

“…34,35,49,50 For our simulations of Aβ 16−22 in AOT RMs, Figure 2 shows the average number of molecules (AOT head groups, AOT tail groups, and sodium ions) within 4 Å of each amino acid side chain of the monomers and dimers, respectively. The number of interactions for the peptides does not change significantly between the monomer and dimer systems, and in both systems there are significant hydrophobic interactions between the V 18 FFA 21 of the Aβ 16−22 peptides and the AOT tail groups.…”

Section: Resultsmentioning

confidence: 99%

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Exploring the role of hydration and confinement in the aggregation of amyloidogenic peptides Aβ16−22 and Sup357−13 in AOT reverse micelles

Martinez

Małolepsza

Rivera

et al. 2014

The Journal of Chemical Physics

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Knowledge of how intermolecular interactions of amyloid-forming proteins cause protein aggregation and how those interactions are affected by sequence and solution conditions is essential to our understanding of the onset of many degenerative diseases. Of particular interest is the aggregation of the amyloid-β (Aβ) peptide, linked to Alzheimer's disease, and the aggregation of the Sup35 yeast prion peptide, which resembles the mammalian prion protein linked to spongiform encephalopathies. To facilitate the study of these important peptides, experimentalists have identified small peptide congeners of the full-length proteins that exhibit amyloidogenic behavior, including the KLVFFAE sub-sequence, Aβ 16−22 , and the GNNQQNY subsequence, Sup35 7−13 . In this study, molecular dynamics simulations were used to examine these peptide fragments encapsulated in reverse micelles (RMs) in order to identify the fundamental principles that govern how sequence and solution environment influence peptide aggregation. Aβ 16−22 and Sup35 7−13 are observed to organize into anti-parallel and parallel β-sheet arrangements. Confinement in the sodium bis(2-ethylhexyl) sulfosuccinate (AOT) reverse micelles is shown to stabilize extended peptide conformations and enhance peptide aggregation. Substantial fluctuations in the reverse micelle shape are observed, in agreement with earlier studies. Shape fluctuations are found to facilitate peptide solvation through interactions between the peptide and AOT surfactant, including direct interaction between non-polar peptide residues and the aliphatic surfactant tails. Computed amide I IR spectra are compared with experimental spectra and found to reflect changes in the peptide structures induced by confinement in the RM environment. Furthermore, examination of the rotational anisotropy decay of water in the RM demonstrates that the water dynamics are sensitive to the presence of peptide as well as the peptide sequence. Overall, our results demonstrate that the RM is a complex confining environment where substantial direct interaction between the surfactant and peptides plays an important role in determining the resulting ensemble of peptide conformations. By extension the results suggest that similarly complex sequence-dependent interactions may determine conformational ensembles of amyloid-forming peptides in a cellular environment. © 2014 AIP Publishing LLC.

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Section: Introductionsupporting

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Exploring the role of hydration and confinement in the aggregation of amyloidogenic peptides Aβ16−22 and Sup357−13 in AOT reverse micelles

Martinez

Małolepsza

Rivera

et al. 2014

The Journal of Chemical Physics

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“…[36][37][38] There are several pioneering experimental and computational studies relating the aggregation properties to the conformations adopted by Aβ peptides upon their interaction with lipids. [39][40][41][42][43][44][45][46][47][48][49][50][51][52] The aggregation process depends on the type of lipids (i.e., neutral or charged), peptide and salt concentrations, and pH. It has been reported that charged lipids induce β-strand structure in Aβ peptides to a similar extent as the increase in their concentration in solution, and that CD spectroscopy measurements can evidence significant (i.e., about 40-60%) β-strand content.…”

Section: Introductionmentioning

confidence: 96%

Molecular Interactions of Alzheimer's Aβ Protofilaments with Lipid Membranes

Tofoleanu

Buchete

2012

Journal of Molecular Biology

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“…3 These properties make RMs powerful tools in which to probe confinement effects and dehydration on biological molecules. 4–6 …”

Section: Introductionmentioning

confidence: 99%

Probing the Structure and Dynamics of Confined Water in AOT Reverse Micelles

et al. 2013

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Reverse micelles are attractive nanoscale systems used for the confinement of molecules in studies of structure and chemical reactions, including protein folding and aggregation. The simulation of reverse micelles, in which a water “pool” is separated from a non-polar bulk phase by a surfactant layer, poses significant challenges to empirical force fields due to the diversity of interactions between non-polar, polar, and charged groups. We have explored the dependence of system density, reverse micelle structure, and water configurational relaxation times as a function of reverse micelle composition, including water:surfactant ratio, absolute number of water molecules, and force field using molecular dynamics simulations. The resulting structures and dynamics are found to depend more on the force field used than on varying interpretations of the water:surfactant ratio in terms of absolute size of the reverse micelle. Substantial deviations from spherical reverse micelle geometries are observed in all unrestrained simulations. Rotational anisotropy decay times and water residence times show a strong dependence of force field and water model used, but power-law relaxation in time is observed independent of the force field. Our results suggest the need for further experimental study of reverse micelles that can provide insight into the distribution and dynamics of shape fluctuations in these complex systems.

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Protein folding in a reverse micelle environment: The role of confinement and dehydration

Cited by 27 publications

References 62 publications

Exploring the role of hydration and confinement in the aggregation of amyloidogenic peptides Aβ16−22 and Sup357−13 in AOT reverse micelles

Exploring the role of hydration and confinement in the aggregation of amyloidogenic peptides Aβ16−22 and Sup357−13 in AOT reverse micelles

Molecular Interactions of Alzheimer's Aβ Protofilaments with Lipid Membranes

Probing the Structure and Dynamics of Confined Water in AOT Reverse Micelles

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