ArticleACS chemical neuroscience2014
Effect of the English familial disease mutation (H6R) on the monomers and dimers of Aβ40 and Aβ42.
Article in ACS chemical neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Survey of the Aβ-peptide structural diversity: molecular dynamics approaches.Biophysical reviews · 2024Review
- Binding mechanism of full-length Aβ40 peptide to a mixed lipid bilayer.Frontiers in chemistry · 2024Article
- Effect of Cholesterol Molecules on Aβ1-42 Wild-Type and Mutants Trimers.Molecules (Basel, Switzerland) · 2022Article
- Dynamics of Amyloid Formation from Simplified Representation to Atomistic Simulations.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Computer Simulations Aimed at Exploring Protein Aggregation and Dissociation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- An Overview of Several Inhibitors for Alzheimer's Disease: Characterization and Failure.International journal of molecular sciences · 2021Review
- Pulsed Hydrogen-Deuterium Exchange Reveals Altered Structures and Mechanisms in the Aggregation of Familial Alzheimer's Disease Mutants.ACS chemical neuroscience · 2021Article
- Impact of Mutations on the Conformational Transition from α-Helix to β-Sheet Structures in Arctic-Type AβACS omega · 2020Article
- Sequence specificity despite intrinsic disorder: How a disease-associated Val/Met polymorphism rearranges tertiary interactions in a long disordered protein.PLoS computational biology · 2019Article
- The combined force field-sampling problem in simulations of disordered amyloid-β peptides.The Journal of chemical physics · 2019Article
- How ARVC-Related Mutations Destabilize Desmoplakin: An MD Study.Biophysical journal · 2019Article
- How Fluorescent Tags Modify Oligomer Size Distributions of the Alzheimer Peptide.Biophysical journal · 2019Article
- Self-assembly of the full-length amyloid Aβ42 protein in dimers.Nanoscale · 2016Article
- Kinetics of the Interactions between Copper and Amyloid-β with FAD Mutations and Phosphorylation at the N terminus.Chembiochem : a European journal of chemical biology · 2016Article
- Critical Nucleus Structure and Aggregation Mechanism of the C-terminal Fragment of Copper-Zinc Superoxide Dismutase Protein.ACS chemical neuroscience · 2016Article
- Allosteric stabilization of the amyloid-β peptide hairpin by the fluctuating N-terminal.Chemical communications (Cambridge, England) · 2016Article
- Effect of pH on the Aggregation of α-syn12 Dimer in Explicit Water by Replica-Exchange Molecular Dynamics Simulation.International journal of molecular sciences · 2015Article
- Coupling of Zinc-Binding and Secondary Structure in Nonfibrillar Aβ40 Peptide Oligomerization.Journal of chemical information and modeling · 2015Article
- Amyloid β Protein and Alzheimer's Disease: When Computer Simulations Complement Experimental Studies.Chemical reviews · 2015Review
- Alzheimer's protective A2T mutation changes the conformational landscape of the Aβ₁₋₄₂ monomer differently than does the A2V mutation.Biophysical journal · 2015Article
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4 authors.
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Abstract
The self-assembly of the amyloid beta (Aβ) peptides into senile plaques is the hallmark of Alzheimer's disease. Recent experiments have shown that the English familial disease mutation (H6R) speeds up the fibril formation process of alloforms Aβ40 and Aβ42 peptides altering their toxicity to cells. We used all-atom molecular dynamics simulations at microsecond time scales with the OPLS-AA force field and TIP4P explicit water model to study the structural dynamics of the monomer and dimer of H6R sequences of both peptides. The reason behind the self-assembly acceleration is common that upon mutation the net charge is reduced leading to the weaker repulsive interaction between chains that facilitates the peptide association. In addition, our estimation of the solvation free energy shows that the mutation enhances the hydrophobicity of both peptides speeding up their aggregation. However, we can show that the acceleration mechanisms are different for different peptides: the rate of fibril formation of Aβ42 increases due to increased β-structure at the C-terminal in both monomer and dimer and enhanced stability of salt bridge Asp23-Lys28 in monomer, while the enhancement of turn at residues 25-29 and reduction of coil in regions 10-13, 26-19, and 30-34 would play the key role for Aβ40. Overall, our study provides a detailed atomistic picture of the H6R-mediated conformational changes that are consistent with the experimental findings and highlights the important role of the N-terminal in Aβ peptide aggregation.
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