Conformational transition of Aβ 42 inhibited by a mimetic peptide. A molecular modeling study using QM/MM calculations and QTAIM analysis

Guisasola, Exequiel Ernesto Barrera; Gutiérrez, Lucas; Salcedo, Rodrigo Emiliano; Garibotto, Francisco Matías; Andújar, Sebastián Antonio; Enriz, Ricardo D.; Rodrı́guez, Ana

doi:10.1016/j.comptc.2016.02.002

Cited by 25 publications

(10 citation statements)

References 71 publications

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“…The binding with (3,3) BNNT is driven by both main-chain and side-chain parts of the hydrophilic N-terminal and CHC residues, whereas major contributions to the peptide binding with BNNS come from hydrophobic side chains of CHC and C-terminal residues, mainly Phe20, Glu22, Asp23, Ile31, Leu34, Met35, val36, Val40, and Ile41. These residues are known to be important in amyloid formation. ,,,− The current study shows that the nanoparticle binding with these hotspot residues can suppress the Aβ aggregation process. The interaction energy of the peptide with BN nanoparticles increases with the increase in the diameter or the decrease in the curvature of the nanoparticle, and this increased interaction energy is found to be responsible for the destabilization of the helical structure of the peptide.…”

Section: Discussionmentioning

confidence: 58%

Interactions of the Aβ(1–42) Peptide with Boron Nitride Nanoparticles of Varying Curvature in an Aqueous Medium: Different Pathways to Inhibit β-Sheet Formation

Sorout

Chandra

2021

J. Phys. Chem. B

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The aggregation of amyloid β (Aβ) peptide triggered by its conformational changes leads to the commonly known neurodegenerative disease of Alzheimer's. It is believed that the formation of β sheets of the peptide plays a key role in its aggregation and subsequent fibrillization. In the current study, we have investigated the interactions of the Aβ(1−42) peptide with boron nitride nanoparticles and the effects of the latter on conformational transitions of the peptide through a series of molecular dynamics simulations. In particular, the effects of curvature of the nanoparticle surface are studied by considering boron nitride nanotubes (BNNTs) of varying diameter and also a planar boron nitride nanosheet (BNNS). Altogether, the current study involves the generation and analysis of 9.5 μs of dynamical trajectories of peptide-BNNT/BNNS pairs in an aqueous medium. It is found that BN nanoparticles of different curvatures that are studied in the present work inhibit the conformational transition of the peptide to its β-sheet form. However, such an inhibition effect follows different pathways for BN nanoparticles of different curvatures. For the BNNT with the highest surface curvature, i.e., (3,3) BNNT, the nanoparticle is found to inhibit β-sheet formation by stabilizing the helical structure of the peptide, whereas for planar BNNS, the β-sheet formation is prevented by making more favorable pathways available for transitions of the peptide to conformations of random coils and turns. The BNNTs with intermediate curvatures are found to exhibit diverse pathways of their interactions with the peptide, but in all cases, essentially no formation of the β sheet is found whereas substantial β-sheet formation is observed for Aβ(1−42) in water in the absence of any nanoparticle. The current study shows that BN nanoparticles have the potential to act as effective tools to prevent amyloid formation from Aβ peptides.

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Section: Discussionmentioning

confidence: 58%

Interactions of the Aβ(1–42) Peptide with Boron Nitride Nanoparticles of Varying Curvature in an Aqueous Medium: Different Pathways to Inhibit β-Sheet Formation

Sorout

Chandra

2021

J. Phys. Chem. B

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“…[ 64 ] This type of calculations has been used in recent works since it ensures a reasonable compromise between the wave function quality required to obtain reliable values of ρ(r) and the computer power available, considering the extension of the system in study. [ 15,65–68 ]…”

Section: Computational Detailsmentioning

confidence: 99%

Evaluating the conformational space of the active site of D₂ dopamine receptor. Scope and limitations of the standard docking methods

et al. 2022

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We report here for the first time the potential energy surfaces (PES) of phenyletilamine (PEA) and meta‐tyramine (m‐OH‐PEA) at the D2 dopamine receptor (D2DR) binding site. PESs not only allow us to observe all the critical points of the surface (minimums, maximums, and transition states), but also to note the ease or difficulty that each local minima have for their conformational inter‐conversions and therefore know the conformational flexibility that these ligands have in their active sites. Taking advantage of possessing this valuable information, we analyze how accurate a standard docking study is in these cases. Our results indicate that although we have to be careful in how to carry out this type of study and to consider performing some extra‐simulations, docking calculations can be satisfactory. In order to analyze in detail the different molecular interactions that are stabilizing the different ligand‐receptor (L‐R) complexes, we carried out quantum theory of atoms in molecules (QTAIM) computations and NMR shielding calculations. Although some of these techniques are a bit tedious and require more computational time, our results demonstrate the importance of performing computational simulations using different types of combined techniques (docking/MD/hybrid QM‐MM/QTAIM and NMR shielding calculations) in order to obtain more accurate results. Our results allow us to understand in details the molecular interactions stabilizing and destabilizing the different L‐R complexes reported here. Thus, the different activities observed for dopamine (DA), m‐OH‐PEA, and PEA can be clearly explained at molecular level.

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“…The origins of the binding affinity between HSV-2 gD and Aβ were shown in Figure 5. The interaction energy less than -2.5 kcalꞏmol -1 of residue with the receptor were considered to be important in binding [14]. As shown in Figure 5, the residues (Glu3, Asp7, Glu11, Val12, Phe19, Glu22, Asp23, Val24, Leu34, Ile41, Ala42) dominated contribution maximum towards binding free energy in the complex.…”

Section: Analysis the Molecular Interaction Between Hsv-1 And Aβ By Mm-pbsamentioning

confidence: 99%

Scrutiny of the mechanism of β-amyloid protein captures HSV-2 to protect the brain infection

Zhang

Wang

2021

E3S Web Conf.

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Alzheimer’s disease (AD) is an age-related neurodegenerative disorder. β-amyloid protein (Aβ) is the key protein which involved in AD. But the physiological function of Aβ is needed to be investigated. Many experimental studies have shown that Aβ could bind to glycoproteins D (gD) on the surface of the herpes virus. However the mechanism is still unclear. In the present study, we elucidate the molecular mechanism of the interaction between Aβ and gD of herpes simplex virus type 2 (HSV-2) by molecular docking and molecular dynamics simulation. Molecular dynamics simulations displayed that Aβ could stably bind to the HSV-2 gD owing to the presence of several interactions. Analysis binding free energy by molecular mechanics Poisson–Boltzmann surface area (MM–PBSA) method revealed that hot residues including Glu3, Glu11, Glu22 and Ala42 of Aβ1-42 were involved in binding with HSV-2 gD. Thus, the HSV-2 gD can be entrapped by Aβ which will be utilized for prevent and therapy of AD in future.

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Conformational transition of Aβ 42 inhibited by a mimetic peptide. A molecular modeling study using QM/MM calculations and QTAIM analysis

Cited by 25 publications

References 71 publications

Interactions of the Aβ(1–42) Peptide with Boron Nitride Nanoparticles of Varying Curvature in an Aqueous Medium: Different Pathways to Inhibit β-Sheet Formation

Interactions of the Aβ(1–42) Peptide with Boron Nitride Nanoparticles of Varying Curvature in an Aqueous Medium: Different Pathways to Inhibit β-Sheet Formation

Evaluating the conformational space of the active site of D₂ dopamine receptor. Scope and limitations of the standard docking methods

Scrutiny of the mechanism of β-amyloid protein captures HSV-2 to protect the brain infection

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Conformational transition of Aβ 42 inhibited by a mimetic peptide. A molecular modeling study using QM/MM calculations and QTAIM analysis

Cited by 25 publications

References 71 publications

Interactions of the Aβ(1–42) Peptide with Boron Nitride Nanoparticles of Varying Curvature in an Aqueous Medium: Different Pathways to Inhibit β-Sheet Formation

Interactions of the Aβ(1–42) Peptide with Boron Nitride Nanoparticles of Varying Curvature in an Aqueous Medium: Different Pathways to Inhibit β-Sheet Formation

Evaluating the conformational space of the active site of D2 dopamine receptor. Scope and limitations of the standard docking methods

Scrutiny of the mechanism of β-amyloid protein captures HSV-2 to protect the brain infection

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Evaluating the conformational space of the active site of D₂ dopamine receptor. Scope and limitations of the standard docking methods