Replica exchange molecular dynamics simulation of the coordination of Pt(<scp>ii</scp>)-Phenanthroline to amyloid-β

Turner, Matthew; Mutter, Shaun T.; Kennedy-Britten, Oliver D.; Platts, James Alexis

doi:10.1039/c9ra04637b

Cited by 5 publications

(2 citation statements)

References 65 publications

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“…However, α_helix and β_sheet are not the only secondary structures. Other secondary structures include Coil, B-Bridge, Bend, and Turn [45]- [47]. α-synuclein protein naturally lacks secondary structures and is an integral part of proteins.…”

Section: Interactions Between Nanoparticles and α-Synuclein And Itsmentioning

confidence: 99%

Potential Treatment of Parkinson's Disease, Using Last-Generation Carbon Nanotubes: A Bimolecular In-Silico Study

Alimohammadi

Nikzad

Khedri

et al. 2020

Preprint

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Background: Parkinson's disease (PD) is one of the most common neurodegenerative disorders. One of the underlying mechanisms of the disease is the accumulation of α-synuclein protein aggregates, including amyloids and Lewy bodies in the brain, resulting in the death of dopaminergic cells in the substantia nigra. The current treatments for PD are mainly focused on replacing dopamine. However, if these medications are stopped, the severity of PD will increase. Moreover, the drugs used for the treatment of PD are associated with considerable side effects and dietary restrictions. Therefore, necessary studies to develop more effective medications for PD seem to be indispensable. To prevent the progression of PD, avoiding the development of α-synuclein amyloids could be proposed. Methods: In this study, the effects of three last-generation nanotube-based structures on α-synuclein amyloid formation were investigated for the first time employing Molecular Dynamics (MD) simulation tools. Molecular dynamics provide a deep insight into atomic interactions and can well study α-synuclein amyloid formation at the atomic and molecular scales.Results: The molecular study results indicated that all of the nanotubes studied in this work, had strong energy interactions with α-synuclein. Therefore, nanotubes using phosphorus, nitrogen and boron dopants, have great potential to prevent α-synuclein amyloid formation. Among these nanotubes, phosphorus-doped carbon nanotube (P-CNT) has the most substantial interactions with α-synuclein. The P-CNT caused more hydrogen bonds to be formed between water and α-synuclein molecules. This phenomenon leads to a decrease in the compactness, stability, and contact area of α-synuclein proteins, which results in considerable changes in the secondary structure of α-synuclein.Conclusions: Doping nanotubes especially P-CNT could be very effective for preventing the α-synuclein amyloid formation and hence, halting the progression of PD. This molecular study paves the way for the use of the Doping nanotubes in the treatment of PD. These structures are highly tunable and flexible. Therefore, the results of this work can be developed to computational, experimental and clinical levels.

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Section: Interactions Between Nanoparticles and α-Synuclein And Itsmentioning

confidence: 99%

Potential Treatment of Parkinson's Disease, Using Last-Generation Carbon Nanotubes: A Bimolecular In-Silico Study

Alimohammadi

Nikzad

Khedri

et al. 2020

Preprint

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“…Similar to the utility of planar hydrophobic moieties discussed in the previous sections, experimental and theoretical modeling studies indicate that the planar hydrophobic phenanthroline ligand is necessary to stabilize His-protein adducts. 99 Binding of a Pt(ϕ-MePy)(DMSO)Cl complex to the Aβ peptide was also shown to change the binding of Cu/Zn to the peptide due to competition for the same metal-binding residues (Fig. 8).…”

Section: Introductionmentioning

confidence: 98%

Targeting misfolding and aggregation of the amyloid-β peptide and mutant p53 protein using multifunctional molecules

Grcic,

Leech,

Kwan

et al. 2024

Chem. Commun.

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The Design of Metal Complexes to Target the Amyloid‐β Peptide in Alzheimer's Disease

Webb

2023

Encyclopedia of Inorganic and Bioinorganic Chemistry

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Alzheimer's disease (AD) is a devastating neurological disorder where a pathological hallmark is the occurrence of amyloid‐β (Aβ) peptide deposits, also known as Aβ plaques. The Aβ peptide is known to self‐associate and aggregate in solution, a phenomenon that is accelerated in the presence of metal ions, in particular Fe, Cu, and Zn. Furthermore, these micronutrient metals are found in elevated concentration within Aβ plaques, relative to nearby healthy tissues. Therapeutic approaches have sought to exploit this metalloprotein nature of Aβ by designing metal complexes that can target either the soluble peptide or its pathological aggregate species. Overall, complexes of 27 different metals have been designed to target the Aβ that can detect its presence in biological samples, modulate its aggregation, and/or prevent its neurotoxic activity. This article summarizes these compounds, and the advances made for complexes of each metal.

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Replica exchange molecular dynamics simulation of the coordination of Pt(ii)-Phenanthroline to amyloid-β

Abstract: Replica exchange molecular dynamics are used to explore the conformational freedom of amyloid-βbound to Pt(phenanthroline), highlighting important differences in secondary and tertiary structure from the metal-free peptide.

Cited by 5 publications

References 65 publications

Potential Treatment of Parkinson's Disease, Using Last-Generation Carbon Nanotubes: A Bimolecular In-Silico Study

Potential Treatment of Parkinson's Disease, Using Last-Generation Carbon Nanotubes: A Bimolecular In-Silico Study

Targeting misfolding and aggregation of the amyloid-β peptide and mutant p53 protein using multifunctional molecules

The Design of Metal Complexes to Target the Amyloid‐β Peptide in Alzheimer's Disease

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