Equilibrium unfolding of the poly(glutamic acid)<sub>20</sub> helix

Finke, John M.; Jennings, Patricia A.; Lee, Jennifer C.; Onuchic, José N.; Winkler, Jay R.

doi:10.1002/bip.20719

Cited by 30 publications

(59 citation statements)

References 78 publications

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“…As with natural proteins, the solution pH, ionic strength, polarity, and peptide concentration can be modulated to adjust the structural conformation from compact α-helix to a variety of “disordered” states [6,7]. WLBU2 is an engineered, c ationic amphiphilic peptide (CAP) with 13 positively-charged arginine residues, and 11 hydrophobic valine or tryptophan residues.…”

Section: Introductionmentioning

confidence: 99%

Structural attributes affecting peptide entrapment in PEO brush layers

Lampi

Schilke

et al. 2013

Colloids and Surfaces B: Biointerfaces

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A more quantitative understanding of peptide loading and release from polyethylene oxide (PEO) brush layers will provide direction for development of new strategies for drug storage and delivery. In this work we recorded selected effects of peptide structure and amphiphilicity on adsorption into PEO brush layers based on covalently stabilized Pluronic®F 108. Optical waveguide lightmode spectroscopy and circular dichroism measurements were used to characterize the adsorption of poly-L-glutamic acid, poly-L-lysine, and the cationic amphiphilic peptide WLBU2, to the brush layers. The structure of WLBU2 as well as that of the similarly-sized homopolymers was controlled between disordered and more ordered (helical) forms by varying solution conditions. Adsorption kinetic patterns were interpreted with reference to a simple model for protein adsorption, in order to evaluate rate constants for peptide adsorption and desorption from loosely and tightly bound states. While more ordered peptide structure apparently promoted faster adsorption and elution rates, resistance to elution while in the PEO layer was dependent on peptide amphiphilicity. The results presented here are compelling evidence of the potential to create anti-fouling surface coatings capable of storing and delivering therapeutics.

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Section: Introductionmentioning

confidence: 99%

Structural attributes affecting peptide entrapment in PEO brush layers

Lampi

Schilke

et al. 2013

Colloids and Surfaces B: Biointerfaces

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“…FRET has been an invaluable approach to study the structural ensemble of unfolded proteins and intrinsically disordered proteins in prior studies 19, 46–66. The present FRET study is modeled after previous successful FRET studies of polyglutamic acid helix‐coil transitions and aggregation 57, 58. As in these previous experiments, the present study used both steady‐state and time‐resolved fluorescence to determine the end‐to‐end distance of the canonical polyglutamine peptide KKQ 16 KK with an aminobenzamide donor at the n‐terminus and nitrotyrosinamide at the c‐terminus (DQ 16 A) 57, 58.…”

Section: Introductionmentioning

confidence: 99%

“…The present FRET study is modeled after previous successful FRET studies of polyglutamic acid helix‐coil transitions and aggregation 57, 58. As in these previous experiments, the present study used both steady‐state and time‐resolved fluorescence to determine the end‐to‐end distance of the canonical polyglutamine peptide KKQ 16 KK with an aminobenzamide donor at the n‐terminus and nitrotyrosinamide at the c‐terminus (DQ 16 A) 57, 58. This end‐to‐end distance will be used, along with previously published donor–acceptor distances determined by FRET, triplet‐state quenching rates, and radius of gyration scaling to assess the accuracy of different theoretical models 19, 25–27.…”

Section: Introductionmentioning

confidence: 99%

An accurate model of polyglutamine

et al. 2011

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Polyglutamine repeats in proteins are highly correlated with amyloid formation and neurological disease. To better understand the molecular basis of glutamine repeat diseases, structural analysis of polyglutamine peptides as soluble monomers, oligomers, and insoluble amyloid fibrils is necessary. In this study, fluorescence resonance energy transfer (FRET) experiments and molecular dynamics simulations using different theoretical models of polyglutamine were conducted. This study demonstrates that a previously proposed simple C(α)C(β) model of polyglutamine, denoted as FCO, accurately reproduced the present FRET results and the results of previously published FRET, triplet-state quenching, and fluorescence correlation studies. Other simple C(α)C(β) models with random coil and extended β-strand parameters, and all-atom models with parm96 and parm99SB force fields, did not match the FRET result well. The FCO is an intrinsically disordered model with a high-effective persistence length producing extended peptides at short lengths (Q(N) < 10). Because of an increasing number of attractive Q-Q interactions at longer lengths, the FCO model becomes increasingly more compact at lengths between Q(N) ∼ 10-16 and is as compact as many folded proteins at Q(N) > 16.

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“…A variety of AH-and BS-based structures have been studied in experiment and molecular dynamics (MD) simulation (10)(11)(12)(13)(14)(15)(16)(17)(18)(19). However, earlier MD simulations were carried out at rather large pulling rates, and therefore, no direct link between simulation and experiment has been reported.…”

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confidence: 99%

Hierarchies, multiple energy barriers, and robustness govern the fracture mechanics of α-helical and β-sheet protein domains

Ackbarow¹,

Chen

Keten³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

195

229

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The fundamental fracture mechanisms of biological protein materials remain largely unknown, in part, because of a lack of understanding of how individual protein building blocks respond to mechanical load. For instance, it remains controversial whether the free energy landscape of the unfolding behavior of proteins consists of multiple, discrete transition states or the location of the transition state changes continuously with the pulling velocity. This lack in understanding has thus far prevented us from developing predictive strength models of protein materials. Here, we report direct atomistic simulation that over four orders of magnitude in time scales of the unfolding behavior of ␣-helical (AH) and ␤-sheet (BS) domains, the key building blocks of hair, hoof, and wool as well as spider silk, amyloids, and titin. We find that two discrete transition states corresponding to two fracture mechanisms exist. Whereas the unfolding mechanism at fast pulling rates is sequential rupture of individual hydrogen bonds (HBs), unfolding at slow pulling rates proceeds by simultaneous rupture of several HBs. We derive the hierarchical Bell model, a theory that explicitly considers the hierarchical architecture of proteins, providing a rigorous structure-property relationship. We exemplify our model in a study of AHs, and show that 3-4 parallel HBs per turn are favorable in light of the protein's mechanical and thermodynamical stability, in agreement with experimental findings that AHs feature 3.6 HBs per turn. Our results provide evidence that the molecular structure of AHs maximizes its robustness at minimal use of building materials.␣-helix ͉ deformation ͉ intermediate filaments ͉ rupture ͉ structure P roteins constitute critical building blocks of life, forming biological materials such as hair, bone, skin, spider silk, or cells (1), displaying highly specific hierarchical structures, from nano to macro. Some of these features are commonly found and highly conserved universal building blocks of protein materials. Examples include ␣-helices (AHs) (1, 2) and ␤-sheets (BSs) (1). Both the AH and BS domains are typically only one of the many domains within a larger protein structure.The AH motif is commonly found in structural protein networks and plays an important role in biophysical processes that involve mechanical signals, including mechanosensation and mechanotransduction, and provide mechanical stability to cells (1-4). For instance, AH-rich intermediate filament networks forward signals from the cellular environment to the DNA (3, 4), aspects that are critical for cell mitosis or apoptosis. The BS motif is an integral component of spider silk, amyloids, and titin (1, 5). The mechanical properties of proteins and the link to associated atomistic-scale chemical reactions are not only of vital importance in biology but are also crucial for the de novo design and manufacturing of protein materials (6-8).Mechanical loading of proteins can result in severe changes in the protein structure, inducing unfolding of the protein....

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Equilibrium unfolding of the poly(glutamic acid)₂₀ helix

Cited by 30 publications

References 78 publications

Structural attributes affecting peptide entrapment in PEO brush layers

Structural attributes affecting peptide entrapment in PEO brush layers

An accurate model of polyglutamine

Hierarchies, multiple energy barriers, and robustness govern the fracture mechanics of α-helical and β-sheet protein domains

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Equilibrium unfolding of the poly(glutamic acid)20 helix

Cited by 30 publications

References 78 publications

Structural attributes affecting peptide entrapment in PEO brush layers

Structural attributes affecting peptide entrapment in PEO brush layers

An accurate model of polyglutamine

Hierarchies, multiple energy barriers, and robustness govern the fracture mechanics of α-helical and β-sheet protein domains

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Equilibrium unfolding of the poly(glutamic acid)₂₀ helix