Molecular dynamics simulation of temperature induced unfolding of animal prion protein

Chen, Xin; Duan, Danhui; Zhu, Shouping; Zhang, Jinglai

doi:10.1007/s00894-013-1955-0

Cited by 12 publications

(14 citation statements)

References 50 publications

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“…The 45–57°C samples significantly increased the unfolding process during aggregation. This was identical to the results using molecular dynamics simulation techniques that elevating temperature could accelerate the unfolding process of prion protein and increase the β ‐sheet structures (Chamachi & Chakrabarty, 2017; Chen et al., 2013). Our data were also in accordance with the molecular dynamics simulation results that the structural conversion of cellular prion protein was triggered by acidic pH (Lu et al., 2013; Thompson et al., 2018).…”

Section: Discussionsupporting

confidence: 83%

“…Like HEWL protein, prion protein can form into amyloid fibrils under acidic pH conditions demonstrated both by experimental studies (Hornemann & Glockshuber, 1998; Singh & Udgaonkar, 2016) and molecular dynamics simulation techniques (Thompson et al., 2018). Elevated temperatures can accelerate the unfolding process and increase the β ‐sheet structures of prion protein using molecular dynamics simulation techniques (Chen et al., 2013; Gu et al., 2003). Hence, HEWL protein and prion protein have similar aggregation‐influencing factors like lower pH and higher temperatures.…”

Section: Introductionmentioning

confidence: 99%

“…Temperatures influence the protein aggregation process (Wang & Roberts, 2018). Many molecular dynamics simulation studies have previously indicated that the different higher temperatures could accelerate the unfolding process and increase the β ‐sheet structures of prion protein by the same mechanisms (Chen et al., 2013; Lee & Chang, 2019). However, due to the inoperability of infectious prion protein, little experimental research has investigated the effect of higher temperatures on the formation of prion amyloid fibrils.…”

Section: Introductionmentioning

confidence: 99%

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Elevated temperatures accelerate the formation of toxic amyloid fibrils of hen egg‐white lysozyme

Feng

Liu

Bai

2021

Veterinary Medicine & Sci

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The formation of amyloid fibrils is critical for neurodegenerative diseases. Some physiochemical conditions can promote the conversion of proteins from soluble globular shapes into insoluble well‐organized amyloid fibrils. The aim of this study was to investigate the effect of temperatures on amyloid fibrils formation in vitro using the protein model of hen egg‐white lysozyme (HEWL). The HEWL fibrils were prepared at temperatures of 37, 45, 50 and 57°C in glycine solution of pH 2.2. Under transmission electron microscopy, we found the well‐organized HEWL amyloid fibrils at temperatures of 45, 50 and 57°C after 10 days of incubation. Thioflavin T and Congo red florescence assays confirmed that the formation and growth of HEWL fibrils displayed a temperature‐dependent increase, and 57°C produced the most amounts. Meanwhile, the surface hydrophobicity of aggregates was greatly increased by ANS binding assay, and β‐sheet contents by circular dichroism analysis were increased by 17.8%, 22.0% and 34.9%, respectively. Furthermore, the HEWL fibrils formed at 57°C caused significant cytotoxicity in SH‐SY5Y cells after 48 hr exposure, and the cell viability determined by MTT assay was decreased, with 81.35 ± 0.29% for 1 μM, 61.45 ± 2.62% for 2 μM, and 11.58 ± 0.39% (p < .01) for 3 μM. Nuclear staining results also confirmed the apoptosis features. These results suggest that the elevated temperatures could accelerate protein unfolding of the native structure and formation of toxic amyloid fibrils, which can improve understanding the mechanisms of the unfolding and misfolding process of prion protein.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Elevated temperatures accelerate the formation of toxic amyloid fibrils of hen egg‐white lysozyme

Feng

Liu

Bai

2021

Veterinary Medicine & Sci

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“…This indicates that (S)-sotolone is a favorable target for OR8D1 and can form stable complexes. 47 The RMSD between each atom of the protein and the rotation axis is expressed as the radius of rotation (R g ), which represents the structural compactness. Throughout the simulation process, a lower and more consistent fluctuation degree increases the rigidity and compactness of the system.…”

Section: Odor Characteristics and Thresholds Of (R)-/(s)-mentioning

confidence: 99%

Decoding Molecular Mechanism Underlying Human Olfactory Receptor OR8D1 Activation by Sotolone Enantiomers

Wang,

Huang

et al. 2024

J. Agric. Food Chem.

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Sotolone, a chiral compound, plays an important role in the food industry. Herein, (R)-/(S)-sotolone were separated to determine their odor characteristics and thresholds in air (R-form: smoky, burned, herb, and green aroma, 0.0514 μg/m3; S-form: sweet, milk, acid, and nutty aroma, 0.0048 μg/m3). OR8D1 responses to (R)-/(S)-sotolone were detected in a HEK293 cell-based luminescence assay. (S)-Sotolone was a more potent agonist than (R)-sotolone (EC50 values of 84.98 ± 1.05 and 167.20 ± 0.25 μmol/L, respectively). Molecular dynamics simulations and molecular mechanics Poisson–Boltzmann surface area analyses confirmed that the combination of (S)-sotolone and OR8D1 was more stable than that of (R)-sotolone. Odorant docking, multiple sequence alignments, site-directed mutagenesis, and functional studies with recombinant odorant receptors (ORs) in a cell-based luminescence assay identified 11 amino-acid residues that influence the enantioselectivity of OR8D1 toward sotolone significantly and that N2065.46 was indispensable to the activation of OR8D1 by (S)-sotolone.

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“…With the rapid development of computer technology, computational biophysics has started to focus on researching the structure and interactions of biomolecules at the atomistic level. It has become another powerful method to discover the inherent mechanisms of molecular biology [ 10 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of the Temperature and Salt Concentration on the Structural Characteristics of the Protein (PDB Code 1BBL)

Shao

Zhang

et al. 2022

Polymers

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The effect of the temperature and salt solution on the structural characteristics of the protein 1BBL was investigated by molecular dynamics simulations. The paper presents simulation results regarding the non-bonded energy and the structural stability of the protein immersed in salt solutions with different concentrations and temperatures. Our work demonstrates that the electrostatic potential energy and van der Waals energy of the system show the opposite changes with the influence of the external environment. Since the electrostatic potential energy changes more obviously, it is dominated in the non-bonding interactions. The structural parameters, such as the root mean square deviation and the radius of gyration, increased initially and decreased afterward with the increase of the salt concentration. The protein presented the loose structure with a relative low stability when it was immersed in a monovalent solution with a salt concentration of 0.8 mol/L. The salt concentration corresponding to the maximum value of structural parameters in the monovalent salt solution was double that in the divalent salt solution. It was also concluded that the protein presented a compact and stable structure when immersed in salt solutions with a high concentration of 2.3 mol/L. The analysis of the root mean square deviation and root mean square fluctuation of the protein sample also exhibited that the structural stability and chain flexibility are strongly guided by the effect of the temperature. These conclusions help us to understand the structural characteristics of the protein immersed in the salt solutions with different concentrations and temperatures.

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Molecular dynamics simulation of temperature induced unfolding of animal prion protein

Cited by 12 publications

References 50 publications

Elevated temperatures accelerate the formation of toxic amyloid fibrils of hen egg‐white lysozyme

Elevated temperatures accelerate the formation of toxic amyloid fibrils of hen egg‐white lysozyme

Decoding Molecular Mechanism Underlying Human Olfactory Receptor OR8D1 Activation by Sotolone Enantiomers

Effects of the Temperature and Salt Concentration on the Structural Characteristics of the Protein (PDB Code 1BBL)

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