Dependence of folding dynamics and structural stability on the location of a hydrophobic pair in β‐hairpins

Imamura, Hideo; Chen, Jeff Z. Y.

doi:10.1002/prot.20846

Cited by 21 publications

(25 citation statements)

References 84 publications

(222 reference statements)

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“…Another important point to address is hydrophobic clustering. Many studies have examined the hydrophobic effect in the stability of β-hairpins: experimental studies [66,73,85], MD simulation [86] and MC simulation [87]. A proper explicit description of the hydrophobic clustering effect will help to clarify its role in cooperativity and the M-WSME model may also benefit from such a description to provide a local view of the hydrophobic effects in the β-hairpin.…”

Section: Discussionmentioning

confidence: 99%

Thermodynamics of protein folding using a modified Wako-Saitô-Muñoz-Eaton model

et al. 2012

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Herein, we propose a modified version of the Wako-Saitô-Muñoz-Eaton (WSME) model. The proposed model introduces an empirical temperature parameter for the hypothetical structural units (i.e., foldons) in proteins to include site-dependent thermodynamic behavior. The thermodynamics for both our proposed model and the original WSME model were investigated. For a system with beta-hairpin topology, a mathematical treatment (contact-pair treatment) to facilitate the calculation of its partition function was developed. The results show that the proposed model provides better insight into the site-dependent thermodynamic behavior of the system, compared with the original WSME model. From this site-dependent point of view, the relationship between probe-dependent experimental results and model's thermodynamic predictions can be explained. The model allows for suggesting a general principle to identify foldon behavior. We also find that the backbone hydrogen bonds may play a role of structural constraints in modulating the cooperative system. Thus, our study may contribute to the understanding of the fundamental principles for the thermodynamics of protein folding.Keywords WSME model · Protein · Beta-hairpin · Backbone hydrogen bond · Thermodynamics · Probe-dependent thermodynamic behavior · Site-dependent behavior · Foldon

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Section: Discussionmentioning

confidence: 99%

Thermodynamics of protein folding using a modified Wako-Saitô-Muñoz-Eaton model

et al. 2012

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“…4 Small oligomers of Aβ peptides are also the focus of many other studies, both computational and experimental ones. [5][6][7][8][9][10][11][12][13][14][15][16] This is because they are likely candidates for the neurotoxic agents in the pathology of Alzheimer's disease while as part of the unsolvable fibrils Aβ peptides appear to be less harmful. This suggests that treatment strategies should aim at decreasing the concentration of harmful oligomers, by either dissolving such oligomers or enhancing fibril growth.…”

Section: Introductionmentioning

confidence: 99%

Replica exchange molecular dynamics of the thermodynamics of fibril growth of Alzheimer's Aβ42 peptide

Han

Hansmann

2011

The Journal of Chemical Physics

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The growth of amyloid fibrils is studied by replica exchange molecular dynamics in an implicit solvent. Our data indicate that extremely long simulation times (at least a few hundred ns) are necessary to study the thermodynamics of fibril elongation in detail. However some aspects of the aggregation process are already accessible on the time scales available in the present study. A peak in the specific heat indicates a docking temperature of T dock ≈ 320 K. Irreversible locking requires lower temperatures with the locking temperature estimated as T lock ≈ 280 K. In our simulation the fibril grows from both sides with the C-terminal of the incoming monomer attaching to the C-terminal of the peptides in the fibril forming a β-sheet on the fibril edge. Our simulation indicates that the C-terminal is crucial for aggregation.

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“…One profusely accepted strategy to overcome this drawback is the use of coarse-grained models. [12][13][14][15] Lowering the level of detail of the protein description allows a faster exploration of the conformational space, losing the specific information of each atom, yet trying to provide a realistic description of the behavior of the protein as a whole.…”

Section: Introductionmentioning

confidence: 99%

A refined hydrogen bond potential for flexible protein models

Enciso

Rey

2010

The Journal of Chemical Physics

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One of the major disadvantages of coarse-grained hydrogen bond potentials, for their use in protein folding simulations, is the appearance of abnormal structures when these potentials are used in flexible chain models, and no other geometrical restrictions or energetic contributions are defined into the system. We have efficiently overcome this problem, for chains of adequate size in a relevant temperature range, with a refined coarse-grained hydrogen bond potential. With it, we have been able to obtain nativelike ␣-helices and ␤-sheets in peptidic systems, and successfully reproduced the competition between the populations of these secondary structure elements by the effect of temperature and concentration changes. In this manuscript we detail the design of the interaction potential and thoroughly examine its applicability in energetic and structural terms, considering factors such as chain length, concentration, and temperature.

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Dependence of folding dynamics and structural stability on the location of a hydrophobic pair in β‐hairpins

Cited by 21 publications

References 84 publications

Thermodynamics of protein folding using a modified Wako-Saitô-Muñoz-Eaton model

Thermodynamics of protein folding using a modified Wako-Saitô-Muñoz-Eaton model

Replica exchange molecular dynamics of the thermodynamics of fibril growth of Alzheimer's Aβ42 peptide

A refined hydrogen bond potential for flexible protein models

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