The WHO has listed Alzheimer's disease among the major neurological disorders with an estimated 35 million people affected worldwide. Amyloid-β is mostly believed to be the causative factor in Alzheimer's disease and the severity of the disease correlates with the tendency of amyloid-β to form aggregation patterns-plaques. Lacking effective medication, the identification of any underlying mechanistic principles regarding plaque formation appears to be crucial. Here we carry out computer simulations to study the effect of C60 on structure and stability of an idealised pentameric construct of amyloid-β units (a model fibril). A binding site on top of the structurally ordered stack of β-sheets is identified that triggers structural alterations at the turn region of the hook-like β-sheet assembly. Significant structural alterations are: (i) the destruction of regular helical twist, (ii) the loss of a stabilizing salt bridge and (iii) the loss of a stabilizing hydrophobic interaction close to the turn. Consequently, the main effect of C60 is the induction of sizable destabilization in native fibril structure. These structural insights may serve as a molecular guide for further rational drug design of effective inhibitors targeting fibril formation in Alzheimer's disease.
The interaction of beta-amyloid (Abeta) peptides with externally applied electric fields (EF) of varying strengths was investigated by means of molecular dynamics (MD) simulations. The results suggest that the EF favors the switch of Abeta-peptides from helical to beta-sheet conformation, and a mechanism is tentatively proposed. Switching off the field does not restore the original conformation.
Artificial self-propelled micro- and nanoengines, or swimmers, have been increasingly attracting the interest of experimental and theoretical groups. They work at low Reynolds number, where inertia does not sustain motion once the driving force stops, and often require complicated chemistry in both structural and dynamical terms. Here we design and investigate computationally with a coarse-grained model some very simple devices, in the form of chemically propelled Janus swimmers, that is, asymmetrical colloidal particles that catalyze the formation of products characterized by poor interactions with part of the body of the particle. The results show that these simple systems display propulsive motion comparable to that of more complicated micro- and nanoscale engines. We also find that in analogy to the behavior of macroscopic motors the particle shape greatly matters and influences not only the random diffusion, as in Stokes–Einstein law, but also the efficiency of the propulsive motion.
We use molecular dynamics to simulate the collapse of nanobubbles in water and show that the macroscopic description holds down to the nanometer size. We further give a description of the collapse in terms of stochastic growth of the density of water inside the cavity. Finally, we address the energy variation in time of the collapse in very simple terms.
Amyloid fibrils are highly ordered protein aggregates, which are associated with many neurodegenerative diseases. The assembling dynamics of monomeric beta-amyloid peptides, Aβ, into small aggregates (and then into long fibrils) is still debated and has become a hot topic. In this study, we conducted molecular dynamics simulations in explicit water of small Aβ protofibrils (from monomer to pentamer) under the perturbation of an externally applied electric field with the aim of investigating the fundamental molecular interactions involved in the aggregation mechanism. Dynamics of small adducts of Aβ(16-42) in the presence of an electric field, which was shown before to accelerate the conformational change of a single molecule, indicate that the structural resilience increases with the number of molecules in the aggregate. In particular, for 50 ns, the pentamer shows an enhanced stability in secondary structure, number of hydrogen bonds, and number of salt bridges, even in the presence of the field perturbation. The resilience to the field perturbation is linked to the variation of the induced dipole moment of the aggregates that tends to level off very rapidly with the growing number of molecules, thereby reducing the energy available per molecule to produce structural changes. The results also show that in the presence of the field the stability of the hydrophobic second β-sheet (β2, residues 31-42) is higher than that of the first one (β1, residues 18-26). In particular, we identify Gly33, Gly37, and Met35 as the most important residues that stabilize the intermolecular packing and may act as nucleation sites for fibrillization. Furthermore, dynamics of the full-length Aβ(1-42) pentameric aggregate, which include the highly charged random coil residues 1-15, confirmed the key role of the second hydrophobic core in the protofibril structure.
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