Recent advances in the development and application of peptide self-assemblies in infection control

Current Opinion in Colloid & Interface Science, Journal Year: 2023, Volume and Issue: 68, P. 101745 - 101745

Published: Aug. 30, 2023

Language: Английский

---

Dissecting how ALS-associated D290V mutation enhances pathogenic aggregation of hnRNPA2286–291 peptides: Dynamics and conformational ensembles

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 241, P. 124659 - 124659

Published: April 27, 2023

Language: Английский

---

Molecular Crowders Can Induce Collapse in Hydrophilic Polymers via Soft Attractive Interactions

The Journal of Physical Chemistry B, Journal Year: 2023, Volume and Issue: 127(28), P. 6265 - 6276

Published: July 6, 2023

A comprehensive understanding of protein folding and biomolecular self-assembly in the intracellular environment requires obtaining a microscopic view crowding effects. The classical explains collapse such an terms entropic solvent excluded volume effects subjected to hard-core repulsions exerted by inert crowders, neglecting their soft chemical interactions. In this study, nonspecific, interactions molecular crowders regulating conformational equilibrium hydrophilic (charged) polymers are examined. Using advanced dynamics simulations, free energies uncharged, negatively charged, charge-neutral 32-mer generic polymer computed. strength polymer–crowder dispersion energy is modulated examine its effect on collapse. results show that preferentially adsorb drive all three polymers. uncharged opposed change solute–solvent interaction but overcompensated favorable entropy as observed hydrophobic However, charged collapses with due reduction dehydration penalty partition interface shield beads. change. for strongly interacting overall energetic decreases since interact beads via cohesive bridging attractions induce These found be sensitive binding sites polymer, they absent or interesting differences thermodynamic driving forces highlight crucial role nature macromolecule well crowder determining equilibria crowded milieu. emphasize should explicitly considered account findings have implications landscapes.

Language: Английский

---

An S-Shaped Aβ42 Cross-β Hexamer Embedded into a Lipid Bilayer Reveals Membrane Disruption and Permeability

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(5), P. 936 - 946

Published: Feb. 9, 2023

The interactions of amyloid oligomers with membranes are known to contribute cellular toxicity. Numerous in vitro experimental studies reported on the insertion different sizes that can induce cell membrane disruption, extract lipids, and form ion-permeable transmembrane pores. current repertoire amyloid-beta (Aβ) membrane-inserted folds was subject high-resolution structure NMR spectroscopy computer simulations is devoid any cross-β fibrillar structure. In this study, we explored dynamics an S-shaped Aβ42 hexamer model inserted into a lipid bilayer by two atomistic molecular simulations. initial characterized hydrophobic residues at central core (residues 17–21, CHC) C-terminus 30–42) embedded membrane. We observed major structural secondary, tertiary, quaternary rearrangements leading distinct species, trimers, accompanied disruption water permeation. show some configurations, but not majority, have CHC exposed solvent. Overall, our computational results offer new perspectives understand relationship between assemblies permeability.

Language: Английский

---

Impact of Amidation on Aβ_25–35 Aggregation

The Journal of Physical Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Toxic oligomeric species are suspected in the etiology of Alzheimer's disease. The full-length Aβ42 can be studied by fragment Aβ25-35 as it retains neurotoxicity. According to experimental studies, amidation carboxyl terminal decreases fibrillation activity while retaining its neurotoxic properties. Our molecular dynamics simulation aggregation trimer from two initial structures (fibril and randomized helical structures) their amidated nonamidated forms. Comparing systems, results suggest that antiparallel chains dominant amide group leads parallel chains. In terms secondary structures, a higher helix content with corresponding decrease β-sheet is observed consequence amidation. Despite variation chain-chain contacts still mediated Gly motif (GxxxG) Ile residues both systems. As neurotoxicity does not change upon amidation, our imply clumping peptides sustained greater contributing factor toxicity than quaternary structures.

Language: Английский

---

Visual Monitoring of Biomolecular Self-Assembly Dynamics and Imaging of Protein Aggregates by Distinct Emission of a Unique Hydrophobic Carbon Dot

The Journal of Physical Chemistry Letters, Journal Year: 2025, Volume and Issue: unknown, P. 3501 - 3508

Published: March 31, 2025

Here, we report a novel and unique application of special hydrophobic carbon dot (HCD) to monitor biomolecular self-assembly, along with the detection metastable intermediates self-aggregates. We exploited restricted rotation S–S bond HCD synthesized from dithiosalicylic acid melamine illuminate different emission behaviors during self-assembly amino acids proteins. The that exhibits blue in droplets or protein aggregates dynamically changes its red over time course process. This distinct change can be visualized by naked eye under UV lamp. ability distinguish self-aggregated structures dynamics utilized for visual uncontrolled aggregation proteins peptides related neurodegenerative diseases like Alzheimer's disease Parkinson's disease.

Language: Английский

---

Metastable alpha‐rich and beta‐rich conformations of small Aβ42 peptide oligomers

Proteins Structure Function and Bioinformatics, Journal Year: 2023, Volume and Issue: unknown

Published: April 10, 2023

Abstract Probing the structures of amyloid‐β (Aβ) peptides in early steps aggregation is extremely difficult experimentally and computationally. Yet, this knowledge important as small oligomers are most toxic species. Experiments simulations on Aβ42 monomer point to random coil conformations with either transient helical or β‐strand content. Our current conformational description funneled toward amorphous aggregates some β‐sheet content rare high energy states well‐ordered assemblies β‐sheets. In study, we emphasize another view based metastable α‐helix bundle spanning C‐terminal residues, which predicted by machine‐learning AlphaFold2 method supported indirectly low‐resolution experimental data many amyloid polypeptides. This finding has consequences developing novel chemical tools design potential therapies reduce toxicity.

Language: Английский

---

Metal Ion-Induced Unusual Stability of the Metastable Vesicle-like Intermediates Evolving during the Self-Assembly of Phenylalanine: Prominent Role of Surface Charge Inversion

The Journal of Physical Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(16), P. 4468 - 4476

Published: April 17, 2024

The underlying mechanism and intermediate formation in the self-assembly of aromatic amino acids, peptides, proteins remain elusive despite numerous reports. We, for first time, report that one can stabilize intermediates by tuning metal ion–amino acid interaction. Microscopic spectroscopic investigations carboxybenzyl (Z)-protected phenylalanine (ZF) reveal bivalent ions eventually lead to fibrillar networks similar blank ZF whereas trivalent develop vesicle-like do not undergo fibrillation a prolonged time. time-lapse measurement surface charge reveals presence changes from negative value zero, implying unstable leading fibril network. Strikingly, prominent inversion an initial positive imparts unusual stability metastable intermediates.

Language: Английский

---

Multistep molecular mechanisms of Aβ16-22 fibril formation revealed by lattice Monte Carlo simulations

The Journal of Chemical Physics, Journal Year: 2023, Volume and Issue: 158(23)

Published: June 15, 2023

As a model of self-assembly from disordered monomers to fibrils, the amyloid-β fragment Aβ16-22 was subject past numerous experimental and computational studies. Because dynamics information between milliseconds seconds cannot be assessed by both studies, we lack full understanding its oligomerization. Lattice simulations are particularly well suited capture pathways fibrils. In this study, explored aggregation 10 peptides using 65 lattice Monte Carlo simulations, each simulation consisting 3 × 109 steps. Based on total 24 41 that converge do not fibril state, respectively, able reveal diversity leading structure conformational traps slowing down formation.

Language: Английский

---

Recent Computational Advances Regarding Amyloid-β and Tau Membrane Interactions in Alzheimer’s Disease

Molecules, Journal Year: 2023, Volume and Issue: 28(20), P. 7080 - 7080

Published: Oct. 13, 2023

The interactions of amyloid proteins with membranes have been subject to many experimental and computational studies, as these contribute in part neurodegenerative diseases. In this review, we report on recent simulations that focused the adsorption insertion modes amyloid-β tau membranes. atomistic-resolution characterization conformational changes upon lipid cell membrane free is interest rationally design drugs targeting transient oligomers Alzheimer’s disease.

Language: Английский

---