Nonequilibrium molecular dynamics simulations of infrared laser-induced dissociation of a tetrameric Aβ42 β-barrel in a neuronal membrane model

Man, Viet Hoang; Wang, Junmei; Derreumaux, Philippe; Nguyen, Phuong H.

doi:10.1016/j.chemphyslip.2020.105030

Cited by 2 publications

(3 citation statements)

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“…Various fibrils from lysozyme (129 residues), insulin (51 residues), DFNKF (5 residues), polyglutamine (69 residues), Aβ (42 residues), GNNQQNY (7 residues), and β2-microglobulin peptide (11 residues) can be dissociated to their non-fibril states, although the disassembly patterns are slightly various depending on the amino acid sequences. In addition, those experimental results were arguably evidenced by molecular dynamic simulations [ 62 , 63 , 64 , 65 , 66 ]. Interestingly, the conversion from β-sheets to α-helices is observed in all types of amyloid proteins.…”

Section: Introductionmentioning

confidence: 81%

“…Regarding the therapeutic strategies for Alzheimer’s disease (AD), non-pharmaceutical approaches are now highly desirable although several antibodies against Aβ and inactivators of γ-secretase have been tested as pharmaceutical drugs [ 78 , 79 , 80 ]. In recent years, it has been suggested that the binding of Aβ to cell membranes is a critical step for the onset of AD pathogenicity, and the hydrophobic interactions of cholesterol molecules with Aβ play important roles in β-sheet oligomerization [ 64 , 81 , 82 , 83 , 84 ]. Therefore, it can be supposed that targeting the binding of cholesterol in the lipid membrane to the Aβ fibril may affect the progression of the pathogenicity.…”

Section: Future Application Of Ir-fel In Amyloid Researchmentioning

confidence: 99%

“…The applications of IR-FEL in the dissociation of amyloid fibrils have been demonstrated for various systems. From the theoretical side, molecular dynamics simulations have been performed for various fibril models, including Aβ 17-42 and HET-s [ 62 ], GNNQQNY fibrils [ 59 ], pure polyglutamine and pure polyasparagine fibrils [ 69 ], and tetrameric Aβ 1-42 β-barrel in neuronal membrane [ 64 ]. From the experimental side, we have investigated the conformational changes of several fibrils from lysozyme [ 21 , 58 ], insulin [ 22 ], DFNKF [ 52 , 53 , 57 ], polyglutamine [ 54 ], Aβ 1-42 [ 56 ], GNNQQNY [ 59 ], and β2-microglobulin [ 60 ] by using infrared microspectroscopy, electron microscopy, and the fibril-binding fluorescent reagents.…”

Section: Introductionmentioning

confidence: 99%

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Disassembly of Amyloid Fibril with Infrared Free Electron Laser

Kawasaki

Tsukiyama

Nguyen

2023

IJMS

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Amyloid fibril causes serious amyloidosis such as neurodegenerative diseases. The structure is composed of rigid β-sheet stacking conformation which makes it hard to disassemble the fibril state without denaturants. Infrared free electron laser (IR-FEL) is an intense picosecond pulsed laser that is oscillated through a linear accelerator, and the oscillation wavelengths are tunable from 3 μm to 100 μm. Many biological and organic compounds can be structurally altered by the mode-selective vibrational excitations due to the wavelength variability and the high-power oscillation energy (10–50 mJ/cm2). We have found that several different kinds of amyloid fibrils in amino acid sequences were commonly disassembled by the irradiation tuned to amide I (6.1–6.2 μm) where the abundance of β-sheet decreased while that of α-helix increased by the vibrational excitation of amide bonds. In this review, we would like to introduce the IR-FEL oscillation system briefly and describe combination studies of experiments and molecular dynamics simulations on disassembling amyloid fibrils of a short peptide (GNNQQNY) from yeast prion and 11-residue peptide (NFLNCYVSGFH) from β2-microglobulin as representative models. Finally, possible applications of IR-FEL for amyloid research can be proposed as a future outlook.

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Section: Introductionmentioning

confidence: 81%

Section: Future Application Of Ir-fel In Amyloid Researchmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Disassembly of Amyloid Fibril with Infrared Free Electron Laser

Kawasaki

Tsukiyama

Nguyen

2023

IJMS

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Dynamics of Amyloid Formation from Simplified Representation to Atomistic Simulations

Nguyen

Tufféry

Derreumaux

2022

Methods in Molecular Biology

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Amyloid fibril formation is an intrinsic property of short peptides, non-disease proteins and proteins associated neurodegenerative diseases. Aggregates of the Aβ and tau proteins, the α-synuclein protein, and the prion protein are observed in the brain of Alzheimer's, Parkinson's and prion disease patients, respectively. Due to the transient short-range and long-range interactions of all species and their high aggregation propensities, the conformational ensemble of these devastating proteins, the exception being for the monomeric prion protein, remains elusive by standard structural biology methods in bulk solution and in lipid membranes. To overcome these limitations, an increasing number of simulations using different sampling methods and protein models have been performed. In this article, we first review our main contributions to the field of amyloid protein simulations aimed at understanding the early aggregation steps of short linear amyloid peptides, the conformational ensemble of the Aβ40/42 dimers in bulk solution, and the stability of Aβ aggregates in lipid membrane models. Then we focus on our studies on the interactions of amyloid peptides/inhibitors to prevent aggregation, and long amyloid sequences, including new results on a monomeric tau construct.

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Nonequilibrium molecular dynamics simulations of infrared laser-induced dissociation of a tetrameric Aβ42 β-barrel in a neuronal membrane model

Cited by 2 publications

References 88 publications

Disassembly of Amyloid Fibril with Infrared Free Electron Laser

Disassembly of Amyloid Fibril with Infrared Free Electron Laser

Dynamics of Amyloid Formation from Simplified Representation to Atomistic Simulations

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