How accurate are your simulations? Effects of confined aqueous volume and AMBER FF99SB and CHARMM22/CMAP force field parameters on structural ensembles of intrinsically disordered proteins: Amyloid-β<sub>42</sub>in water

Coskuner‐Weber, Orkid; Uversky, Vladimir N.

doi:10.1080/21690707.2017.1377813

Cited by 39 publications

(31 citation statements)

References 129 publications

(203 reference statements)

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“…76 The peptide was inserted into the dodecahedron periodic boundary condition box with a size of ∼310 nm 3 referring to previous works. 77,78 Water molecules were treated by a TIP3P model 79 and four Na + ions were used to keep neutralization of the system. The soluble system was consisted of approximately 31 000 atoms.…”

Section: Materials and Methodsmentioning

confidence: 99%

C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ_11–42 Tetramer in Solution: Intensive MD Study

Tùng

Derreumaux

et al. 2019

ACS Omega

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Amyloid beta (Aβ) peptides are characterized as the major factors associated with neuron death in Alzheimer’s disease, which is listed as the most common form of neurodegeneration. Disordered Aβ peptides are released from proteolysis of the amyloid precursor protein. The Aβ self-assembly process roughly takes place via five steps: disordered forms → oligomers → photofibrils → mature fibrils → plaques. Although Aβ fibrils are often observed in patient brains, oligomers were recently indicated to be major neurotoxic elements. In this work, the neurotoxic compound S-shape Aβ 11–42 tetramer (S4Aβ 11–42 ) was investigated over 10 μs of unbiased MD simulations. In particular, the S4Aβ 11–42 oligomer adopted a high dynamics structure, resulting in unsuccessful determination of their structures in experiments. The C-terminal was suggested as the possible nucleation of the Aβ 42 aggregation. The sequences 27–35 and 39–40 formed rich β-content, whereas other residues mostly adopted coil structures. The mean value of the β-content over the equilibrium interval is ∼42 ± 3%. Furthermore, the dissociation free energy of the S4Aβ 11–42 peptide was predicted using a biased sampling method. The obtained free energy is Δ G US = −58.44 kcal/mol which is roughly the same level as the corresponding value of the U-shape Aβ 17-42 peptide. We anticipate that the obtained S4Aβ 11–42 structures could be used as targets for AD inhibitor screening over the in silico study.

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Section: Materials and Methodsmentioning

confidence: 99%

C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ_11–42 Tetramer in Solution: Intensive MD Study

Tùng

Derreumaux

et al. 2019

ACS Omega

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“…Thermodynamic trends are not affected by the usage of implicit or explicit water models. Following recent studies, the thermodynamic properties were investigated using the molecular mechanics/Poisson-Boltzmann surface area method and potential of mean force surfaces (83,85,86,88,96,(108)(109)(110)(111)(112). For the potential of mean force (PMF) surfaces, the coordinates of the end-toend distances were used along with the radius of gyration values (56,83,85,96,108,109).…”

Section: Replica Exchange Molecular Dynamicsmentioning

confidence: 99%

“…Using the potential functions for Cu:His3Glu, the structures and thermodynamic properties of Cu:His3Glu bound Cu(II):Aβ40 and Cu(II):Aβ42 in an aqueous solution environment using a continuum model for water were studied (85). Recent studies using an explicit model for water show that the confined aqueous volume has a significant impact on the structural and thermodynamic properties of the full-length Aβ peptide (86). In addition, there are studies that report the physical, biological and chemical characteristics of Cu(II):Aβ utilizing smaller fragments instead of using full-length metalloproteins (87).…”

Section: Introductionmentioning

confidence: 99%

Revisiting Cu(II) Bound Amyloid-β40 and Amyloid-β42 Peptides: Varying Coordination Chemistries

Coskuner‐Weber¹

2018

Journal of the Turkish Chemical Society Section A: Chemistry

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Metal ions and intrinsically disordered peptides amyloid-β40 and amyloid-β42 are at the center of Alzheimer´s disease pathology. Divalent copper ion binds to amyloid-β40 and amyloid-β42 peptides with varying coordination chemistries. Experiments face challenges in the measurements of divalent copper ion bound monomeric amyloid-β40 and amyloid-β42 in an aqueous solution medium because of fast conformational changes, rapid aggregation processes and solvent effects. Theoretical studies complement experiments and provide insights at the atomic and molecular levels with dynamics. However, until recently, potential functions for simulating divalent copper ion bound amyloid-β40 and amyloid-β42 peptides with varying coordination chemistries were lacking. Using new potential functions that were developed for divalent copper centers, Cu(II), including three histidine residues and an oxygen-ligated amino acid residue, the structures and thermodynamic properties of Cu(II)-bound amyloid-β40 and amyloid-β42 peptides in an aqueous solution medium were studied. For these purposes, extensive first principles calculations and replica exchange molecular dynamics simulations were conducted. In this study, the secondary and tertiary structural properties, conformational Gibbs free energy values, potential of mean force surfaces, salt bridges and aggregation propensities of aqueous Cu(II)-bound amyloid-β40 and amyloid-β42 peptides are presented. Different than previous findings in the literature, results clearly show that the coordination chemistry variations impact the structural and thermodynamic properties of divalent Cu(II) bound amyloid-β alloforms in water. Specificities about these differences are revealed in this study at the atomic level with dynamics. Results presented herein are the first to offer a comparison of the monomeric Cu(II)-bound amyloid-β40 and amyloid-β42 peptides with varying coordination chemistries using bonded model potential functions.

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“…We used the molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) method to calculate the binding free energy . Considering the simulation accuracy, we employed the Amber ff99SB force field. One hundred snapshots were selected equally every 7 ns after the first 30 ns from the trajectory to calculate the free energy .…”

Section: Methodsmentioning

confidence: 99%

Effects of Tyr555 and Trp678 on the processivity of cellobiohydrolase A from Ruminiclostridium thermocellum: A simulation study

et al. 2018

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Cellobiohydrolase A from Ruminiclostridium thermocellum (Cbh9A) is a processive exoglucanase from family 9 and is an important cellobiohydrolase that hydrolyzes cello‐oligosaccharide into cellobiose. Residues Tyr555 and Trp678 considerably affect catalytic activity, but their mechanisms are still unknown. To investigate how the Tyr555 and Trp678 affect the processivity of Cbh9A, conventional molecular dynamics, steered molecular dynamics, and free energy calculation were performed to simulate the processive process of wild type (WT)‐Cbh9A, Y555S mutant, and W678G mutant. Analysis of simulation results suggests that the binding free energies between the substrate and WT‐Cbh9A are lower than those of Y555S and W678G mutants. The pull forces and energy barrier in Y555S and W678G mutants also reduced significantly during the steered molecular dynamics (SMD) simulation compared with that of the WT‐Cbh9A. And the potential mean force calculations showed that the pulling energy barrier of Y555S and W678G mutants is much lower than that of WT‐Cbh9A.

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How accurate are your simulations? Effects of confined aqueous volume and AMBER FF99SB and CHARMM22/CMAP force field parameters on structural ensembles of intrinsically disordered proteins: Amyloid-β₄₂in water

Cited by 39 publications

References 129 publications

C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ_11–42 Tetramer in Solution: Intensive MD Study

C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ_11–42 Tetramer in Solution: Intensive MD Study

Revisiting Cu(II) Bound Amyloid-β40 and Amyloid-β42 Peptides: Varying Coordination Chemistries

Effects of Tyr555 and Trp678 on the processivity of cellobiohydrolase A from Ruminiclostridium thermocellum: A simulation study

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How accurate are your simulations? Effects of confined aqueous volume and AMBER FF99SB and CHARMM22/CMAP force field parameters on structural ensembles of intrinsically disordered proteins: Amyloid-β42in water

Cited by 39 publications

References 129 publications

C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ11–42 Tetramer in Solution: Intensive MD Study

C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ11–42 Tetramer in Solution: Intensive MD Study

Revisiting Cu(II) Bound Amyloid-β40 and Amyloid-β42 Peptides: Varying Coordination Chemistries

Effects of Tyr555 and Trp678 on the processivity of cellobiohydrolase A from Ruminiclostridium thermocellum: A simulation study

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How accurate are your simulations? Effects of confined aqueous volume and AMBER FF99SB and CHARMM22/CMAP force field parameters on structural ensembles of intrinsically disordered proteins: Amyloid-β₄₂in water

C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ_11–42 Tetramer in Solution: Intensive MD Study

C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ_11–42 Tetramer in Solution: Intensive MD Study