Role of Charge and Solvation in the Structure and Dynamics of Alanine-Rich Peptide AKA<sub>2</sub> in AOT Reverse Micelles

Martinez, Anna Victoria; Małolepsza, Edyta; Domı́nguez, Laura; Lü, Qing; Straub, John E.

doi:10.1021/jp508813n

Cited by 9 publications

(5 citation statements)

References 54 publications

(148 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In more recent work, we calculated IR spectra of AKA 2 peptides in spherically restrained and unrestrained RMs. 35 The computed spectra were in good agreement with experimentally measured spectra for AKA 2 peptides in RMs. 17 The results validate our simulation model of AOT RMs and suggest that probing the features of these complex systems using simulation studies is an essential complement to experiment.…”

Section: Introductionsupporting

confidence: 79%

“…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%

See 1 more Smart Citation

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionsupporting

confidence: 79%

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…The MD simulations of Straub and co-workers 67 provided further atomistic details of the above-mentioned peptide system in spherically restrained and unrestrained RMs of w 0 = 6. They found that α-helical structure was stable under both conditions, consistent with the experimental observation.…”

Section: The Journal Of Physical Chemistry Lettersmentioning

confidence: 99%

“…MD snapshots of an alanine-based peptide in a spherically restrained (left, pink) and a spherically unrestrained (right, green) RM, showing the interaction between the peptide, the surrounding water molecules (blue), and the AOT tail groups (gray). Reprinted with permission from ref . Copyright 2014, American Chemical Society.…”

mentioning

confidence: 99%

Biomolecular Crowding Arising from Small Molecules, Molecular Constraints, Surface Packing, and Nano-Confinement

Hilaire

Abaskharon

Gai

2015

J. Phys. Chem. Lett.

View full text Add to dashboard Cite

The effect of macromolecular crowding on the structure, dynamics, and reactivity of biomolecules is well-established and the relevant research has been extensively reviewed. Herein, we focus our discussion on crowding effects arising from small co-solvent molecules and densely packed surface conditions. In addition, we highlight recent efforts that capitalize on the excluded volume effect for various tailored biochemical and biophysical applications. Specifically, we discuss how a targeted increase in local mass density can be exploited to gain insight into the folding dynamics of the protein of interest and how confinement via reverse micelles can be used to study a range of biophysical questions, from protein hydration dynamics to amyloid formation.

show abstract

“…Tian and Garcia explored the dynamics and location of proteins in RMs 39 and the effect of RMs on the ubiquitin structure and dynamics. 40 Straub and co-workers explored the effect of charged and zwitterionic termini on a RM-spanning protein on the structure and dynamics of RMs 41 as well as the effect of RM-encapsulation on amyloidogenic peptide aggregation. 42 Eskici and Axelsen also investigated the role of RM-encapsulation on the structure of amyloid beta.…”

Section: Introductionmentioning

confidence: 99%

Characterization of dynamics and mechanism in the self-assembly of AOT reverse micelles

Urano

Pantelopulos

Song

et al. 2018

The Journal of Chemical Physics

Self Cite

View full text Add to dashboard Cite

Reverse micelles (RMs) are recognized as a paradigm of molecular self-assembly and used in a variety of applications, such as chemical synthesis and molecular structure refinement. Nevertheless, many fundamental properties including their equilibrium size distribution, internal structure, and mechanism of self-assembly remain poorly understood. To provide an enhanced microscopic understanding of the assembly process and resulting structural distribution, we perform multiple nonequilibrium molecular dynamics simulations of dioctyl sulfosuccinate sodium salt (AOT) RM assembly, quantifying RM size, water core structure, and dynamics. Rapid assembly of smaller RM from a random mixture is observed to establish a constant AOT water loading within a nanosecond consistent with a diffusion-adsorption mechanism validated through the Monte-Carlo simulation of a model system. The structure of RM water cores and RM molecular volume during RM assembly is characterized during the AOT assembly process. A moment-closure equation is developed from a novel master equation model to elucidate the elementary events underlying the AOT selfassembly process. The resulting kinetic model is used to explore the role of monomer addition and dissociation, RM association and dissociation, and RM collision-induced exchange, all dependent on average RM size, which provides fundamental insight regarding the mechanisms and time scales for AOT RM self-assembly. The nascent dynamics that rapidly establish water loading, intermediate time scales of RM fusion, and longer time scale dynamics of inter-RM exchange essential in establishing the equilibrium condition are quantified through these kinetic models. Overall, this work provides insight into AOT RM self-assembly and provides a general theoretical framework for the analysis of the molecular self-assembly dynamics and mechanism.

show abstract

Role of Charge and Solvation in the Structure and Dynamics of Alanine-Rich Peptide AKA₂ in AOT Reverse Micelles

Cited by 9 publications

References 54 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

Biomolecular Crowding Arising from Small Molecules, Molecular Constraints, Surface Packing, and Nano-Confinement

Characterization of dynamics and mechanism in the self-assembly of AOT reverse micelles

Contact Info

Product

Resources

About

Role of Charge and Solvation in the Structure and Dynamics of Alanine-Rich Peptide AKA2 in AOT Reverse Micelles

Cited by 9 publications

References 54 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

Biomolecular Crowding Arising from Small Molecules, Molecular Constraints, Surface Packing, and Nano-Confinement

Characterization of dynamics and mechanism in the self-assembly of AOT reverse micelles

Contact Info

Product

Resources

About

Role of Charge and Solvation in the Structure and Dynamics of Alanine-Rich Peptide AKA₂ in AOT Reverse Micelles