Propensity to form amyloid fibrils is encoded as excitations in the free energy landscape of monomeric proteins.
@article{Zhuravlev2014PropensityTF, title={Propensity to form amyloid fibrils is encoded as excitations in the free energy landscape of monomeric proteins.}, author={Pavel I Zhuravlev and Govardhan Reddy and John E. Straub and D. Thirumalai}, journal={Journal of molecular biology}, year={2014}, volume={426 14}, pages={ 2653-66 } }
47 Citations
Differences in the free energies between the excited states of Aβ40 and Aβ42 monomers encode their distinct aggregation propensities
- ChemistrybioRxiv
- 2020
The N* theory explains the emergence of fibril polymorphs, and predicts the relative kinetic stabilities of Aβ42 fibrils using Ostwald’s rule of stages, shows that sequence-specific conformational heterogeneity of the monomer ensembles provides important cues for understanding protein aggregation.
Different Force Fields Give Rise to Different Amyloid Aggregation Pathways in Molecular Dynamics Simulations.
- Biology, ChemistryJournal of chemical information and modeling
- 2020
A main finding is that changing the force field has a stronger effect on the simulated aggregation pathway than changing the peptide sequence, and the new force fields are not able to reproduce the experimental aggregation propensity order of the peptides, so it is recommended to use this force field for peptide aggregation simulations and base future reparameterizations on it.
A Transient Intermediate Populated in Prion Folding Leads to Domain Swapping.
- BiologyBiochemistry
- 2019
This study proposes a plausible runaway domain swapping mechanism to describe the onset of prion aggregation and finds that these proteins sparsely populate intermediate states bearing the features of N* and readily undergo domain-swapped dimerization by swapping the short β-strands present at the beginning of the C-terminal domain.
Aggregation rate of amyloid beta peptide is controlled by beta-content in monomeric state.
- BiologyThe Journal of chemical physics
- 2019
This study has solved a long-standing problem of the dependence of fibril formation time of the β-structure on a quantitative level by computed β of 19 mutations of amyloid beta peptide of 42 residues for which the aggregation rate κ has been measured experimentally.
On the Applicability of Force Fields To Study the Aggregation of Amyloidogenic Peptides Using Molecular Dynamics Simulations.
- Biology, ChemistryJournal of chemical theory and computation
- 2018
The oligomer formation kinetics obtained with different force fields differ more from each other than the kinetics between aggregating and nonaggregating peptides simulated with a single force field.
A Transient Intermediate Populated in Prion Folding Leads to Domain Swapping
- BiologybioRxiv
- 2019
This study proposes a plausible runaway domain swapping mechanism to describe the onset of prion aggregation, indicating a common pathogenic precursor across diferent species.
Different force fields give rise to different amyloid aggregation pathways in molecular dynamics simulations
- Biology, ChemistrybioRxiv
- 2020
A main finding is that changing the force field has a stronger effect on the simulated aggregation pathway than changing the peptide sequence, and the new force fields are not able to reproduce the experimental aggregation propensity order of the peptides.
Low force unfolding of a single-domain protein by parallel pathways
- BiologybioRxiv
- 2020
Simulations using the SOP-SC model and previous theoretical and experimental studies show that parallel unfolding of structurally unrelated single domain proteins can be determined from the dependence of log ku(f) as a function of force.
pH Induced Switch in the Conformational Ensemble of an Intrinsically Disordered Protein Prothymosin-α and Its Implications to Amyloid Fibril Formation
- Biology, ChemistrybioRxiv
- 2022
The main result upon pH change from neutral to acidic, the intermediate region of proTα is responsible for aggregation due to an increase in its β-sheet forming propensity and forms the fibril core can be verified by experiments.
Amyloid Formation by Human Carboxypeptidase D Transthyretin-like Domain under Physiological Conditions*
- BiologyThe Journal of Biological Chemistry
- 2014
It is shown that the monomeric transthyretin-like domain of human carboxypeptidase D aggregates under close to physiological conditions into amyloid structures, with the population of folded but aggregation-prone states being controlled by the conformational stability of the domain.
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