Communication: Simulated tempering with fast on-the-fly weight determination

Nguyen, Phuong H.; Okamoto, Yuko; Derreumaux, Philippe

doi:10.1063/1.4792046

Cited by 48 publications

(91 citation statements)

References 27 publications

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“…Figure 3 shows the population distributions of the distances between the Lys28-Glu22 and Lys28-Asp23 residues. 42 -D7N only Asp1-Arg5 has a significant lifetime (48%), Lys16-Asn7 and Asp1-Lys16 being formed with lifetimes of 4% and 7%. As for Aβ 40 , there is an interplay between the salt bridges upon D7N mutation.…”

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confidence: 99%

“…30 We also determine how our results fit with available low resolution experimental data from CD analysis and ion-mobility-based mass spectrometry and previous simulations of Aβ-WT monomers and dimers. Recently, the monomeric conformations of Aβ 40 -WT and Aβ 42 -WT were reevaluated by all-atom REMD 41 and MD, 44 but the resulting equilibrium ensembles are rather divergent from each other and from previous simulations. 32,45 The Aβ 40/42 -WT monomer and dimer were also studied by all-atom Monte Carlo simulations with an implicit solvent model 36 and the coarse-grained OPEP model coupled to REMD.…”

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confidence: 99%

“…Impact of D7N on the Secondary Structures, Salt Bridge Populations and Collision Cross Sections of Aβ 40 and Aβ 42 Monomers. The mean and standard deviation of secondary structures of the four monomers are reported in Table 1.…”

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confidence: 99%

“…7,8 The Aβ peptides are proteolytic byproducts of the amyloid precursor protein and are most commonly composed of 40 (Aβ 40 ) and 42 (Aβ 42 ) amino acids. The Aβ monomers are mostly random coil in physiological buffers, but aggregate to form amyloid fibrils with a cross-β-sheet pattern.…”

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confidence: 99%

“…Our goal is not to determine the equilibrium structures of the WT and D7N monomers and dimers for both alloforms. 37 Much longer time scales are required using all-atom MD 33 or we must resort to enhanced conformational techniques such as replica exchange molecular dynamics (REMD), 35,38−41 simulated tempering, 42 or discontinuous molecular dynamics (DMD). 43 In addition, repeating these extensive simulations on a total of eight systems is out of reach using standard computer resources.…”

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confidence: 99%

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Effect of the Tottori Familial Disease Mutation (D7N) on the Monomers and Dimers of Aβ₄₀and Aβ₄₂

Man

Nguyen

Ngo

et al. 2013

ACS Chem. Neurosci.

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ABSTRACT:Recent experiments have shown that the mutation Tottori (D7N) alters the toxicity, assembly and rate of fibril formation of the wild type (WT) amyloid beta (Aβ) Aβ 40 and Aβ 42 peptides. We used all-atom molecular dynamics simulations in explicit solvent of the monomer and dimer of both alloforms with their WT and D7N sequences. The monomer simulations starting from a random coil and totaling 3 μs show that the D7N mutation changes the fold and the network of salt bridges in both alloforms. The dimer simulations starting from the amyloid fibrillar states and totaling 4.4 μs also reveal noticeable changes in terms of secondary structure, salt bridge, and topology. Overall, this study provides physical insights into the enhanced rate of fibril formation upon D7N mutation and an atomic picture of the D7N-mediated conformational change on Aβ 40 and Aβ 42 peptides. KEYWORDS: Amyloid simulation, Alzheimer's disease, amyloid-β proteins, molecular dynamics, D7N mutation, monomer, dimer A lzheimer's disease (AD) is the most common form of dementia among the senior population.1 The patient with AD will lose memory, 2 decay language, 3 and experience problems with visual-spatial search, 4 among other side-effects. AD is pathologically characterized by brain lesions that are senile plaques made of the beta amyloid (Aβ) peptides 5 and neurofibrillary tangles inside neurons made of the tau protein. 6 However, there is strong evidence that the Aβ peptides play a central role in AD. 7,8 The Aβ peptides are proteolytic byproducts of the amyloid precursor protein and are most commonly composed of 40 (Aβ 40 ) and 42 (Aβ 42 ) amino acids. The Aβ monomers are mostly random coil in physiological buffers, but aggregate to form amyloid fibrils with a cross-β-sheet pattern. 9−11Presently, there are no efficient drugs against AD. One current strategy, based on the fact that the aesthetic of the cerebral defects in AD correlates with high levels of oligomers in the brain, 12,13 is to design molecules preventing amyloid fibril formation and targeting the early formed toxic aggregates. 5,7,14−18 The another strategy is to design molecules enhancing fibril formation and reducing therefore the lifetimes of Aβ oligomers. 19 Unfortunately, because these assemblies are in dynamic equilibrium, experiments have failed thus far to provide atomic structures that would help design more efficient molecules in both scenarios.Numerous pathogenic familial mutations are known to modulate fibril formation rates and enhance toxicity. There has been many experimental studies on the Flemish (A21G), Dutch (E22Q), Italian (E22K), Arctic (E22G), Iowa (D23N), and Osaka (ΔE22, deletion) variants. 20−25 The English (H6R), 26Taiwanese (D7H), 27 and Tottori (D7N) 28 mutations that cause early onset familial AD have also been reported. The English and Tottori mutations do not affect Aβ production, but they accelerate fibril assembly in the absence of increased protofibril formation.29 A more recent experimental study showed that the Tottori mutation alters ...

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Effect of the Tottori Familial Disease Mutation (D7N) on the Monomers and Dimers of Aβ₄₀and Aβ₄₂

Man

Nguyen

Ngo

et al. 2013

ACS Chem. Neurosci.

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Simulated tempering based on global balance or detailed balance conditions: Suwa–Todo, heat bath, and Metropolis algorithms

Mori

Okumura

2015

J Comput Chem

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Simulated tempering (ST) is a useful method to enhance sampling of molecular simulations. When ST is used, the Metropolis algorithm, which satisfies the detailed balance condition, is usually applied to calculate the transition probability. Recently, an alternative method that satisfies the global balance condition instead of the detailed balance condition has been proposed by Suwa and Todo. In this study, ST method with the Suwa-Todo algorithm is proposed. Molecular dynamics simulations with ST are performed with three algorithms (the Metropolis, heat bath, and Suwa-Todo algorithms) to calculate the transition probability. Among the three algorithms, the Suwa-Todo algorithm yields the highest acceptance ratio and the shortest autocorrelation time. These suggest that sampling by a ST simulation with the Suwa-Todo algorithm is most efficient. In addition, because the acceptance ratio of the Suwa-Todo algorithm is higher than that of the Metropolis algorithm, the number of temperature states can be reduced by 25% for the Suwa-Todo algorithm when compared with the Metropolis algorithm.

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On the use of mass scaling for stable and efficient simulated tempering with molecular dynamics

et al. 2016

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Simulated tempering (ST) is a generalized-ensemble algorithm that employs trajectories exploring a range of temperatures to effectively sample rugged energy landscapes. When implemented using the molecular dynamics method, ST can require the use of short time steps for ensuring the stability of trajectories at high temperatures. To address this shortcoming, a mass-scaling ST (MSST) method is presented in which the particle mass is scaled in proportion to the temperature. Mass scaling in the MSST method leads to velocity distributions that are independent of temperature and eliminates the need for velocity scaling after the accepted temperature updates that are required in conventional ST simulations. The homogeneity in time scales with changing temperature improves the stability of simulations and allows for the use of longer time steps at high temperatures. As a result, the MSST is found to be more efficient than the standard ST method, particularly for cases in which a large temperature range is employed. © 2016 Wiley Periodicals, Inc.

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Communication: Simulated tempering with fast on-the-fly weight determination

Abstract: International audienceno abstrac

Cited by 48 publications

References 27 publications

Effect of the Tottori Familial Disease Mutation (D7N) on the Monomers and Dimers of Aβ₄₀and Aβ₄₂

Effect of the Tottori Familial Disease Mutation (D7N) on the Monomers and Dimers of Aβ₄₀and Aβ₄₂

Simulated tempering based on global balance or detailed balance conditions: Suwa–Todo, heat bath, and Metropolis algorithms

On the use of mass scaling for stable and efficient simulated tempering with molecular dynamics

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Communication: Simulated tempering with fast on-the-fly weight determination

Abstract: International audienceno abstrac

Cited by 48 publications

References 27 publications

Effect of the Tottori Familial Disease Mutation (D7N) on the Monomers and Dimers of Aβ40and Aβ42

Effect of the Tottori Familial Disease Mutation (D7N) on the Monomers and Dimers of Aβ40and Aβ42

Simulated tempering based on global balance or detailed balance conditions: Suwa–Todo, heat bath, and Metropolis algorithms

On the use of mass scaling for stable and efficient simulated tempering with molecular dynamics

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Product

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Effect of the Tottori Familial Disease Mutation (D7N) on the Monomers and Dimers of Aβ₄₀and Aβ₄₂

Effect of the Tottori Familial Disease Mutation (D7N) on the Monomers and Dimers of Aβ₄₀and Aβ₄₂