Molecular Dynamics Simulation Studies on the Aggregation of Amyloid-β Peptides and Their Disaggregation by Ultrasonic Wave and Infrared Laser Irradiation

Alzheimer’s disease is understood to be caused by amyloid fibrils and oligomers formed by aggregated amyloid-β (Aβ) peptides. This review article presents molecular dynamics (MD) simulation studies of Aβ peptides and Aβ fragments on their aggregation, aggregation inhibition, amyloid fibril conformations in equilibrium, and disruption of the amyloid fibril by ultrasonic wave and infrared laser irradiation. In the aggregation of Aβ, a β-hairpin structure promotes the formation of intermolecular β-sheet structures. Aβ peptides tend to exist at hydrophilic/hydrophobic interfaces and form more β-hairpin structures than in bulk water. These facts are the reasons why the aggregation is accelerated at the interface. We also explain how polyphenols, which are attracting attention as aggregation inhibitors of Aβ peptides, interact with Aβ. An MD simulation study of the Aβ amyloid fibrils in equilibrium is also presented: the Aβ amyloid fibril has a different structure at one end from that at the other end. The amyloid fibrils can be destroyed by ultrasonic wave and infrared laser irradiation. The molecular mechanisms of these amyloid fibril disruptions are also explained, particularly focusing on the function of water molecules. Finally, we discuss the prospects for developing treatments for Alzheimer’s disease using MD simulations.     

Ingenuity in performing replica permutation: How to order the state labels for improving sampling efficiency

In the replica-permutation method, an advanced version of the replica-exchange method, all combinations of replicas and parameters are considered for parameter permutation, and a list of all the combinations is prepared. Here, we report that the temperature transition probability depends on how the list is created, especially in replica permutation with solute tempering (RPST). We found that the transition probabilities decrease at large replica indices when the combinations are sequentially assigned to the state labels as in the originally proposed list. To solve this problem, we propose to modify the list by randomly assigning the combinations to the state labels. We performed molecular dynamics simulations of amyloid-β(16–22) peptides using RPST with the “randomly assigned” list (RPST-RA) and RPST with the “sequentially assigned” list (RPST-SA). The results show the decreases in the transition probabilities in RPST-SA are eliminated, and the sampling efficiency is improved in RPST-RA.     

Nanostructures formed by combination of nanotube and polymer chain

We have investigated polymeric supramolecular systems of inclusion complexes between molecular nanotube and polymer chains theoretically and experimentally. This system indicates inclusion-dissociation behavior much sharper than the inclusion complex between cyclic molecule and small compounds. And we propose some functional supramolecules utilizing the combination of the nanotube or nanoring and polymer chains such as insulated molecular wire and topological gel.     

Syntheses of 2‐alkylthio‐1,3‐thiazine derivatives from S‐alkyldithiocarbamates and α,β‐unsaturated ketones

Various 2‐alkylthio‐1,3‐thiazine derivatives were synthesized by the reactions of S‐alkylthiocarbamates with α,β‐unsaturated ketones in the presence of BF₃ · Et₂O. The thiazine was converted into two isomeric dehydrated products in the presence of a Lewis acid. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:377–379, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10055     

Complex Formation Between Poly(dimethylsilane) and Cyclodextrins

Poly(dimethylsilane)s form inclusion complexes with cyclodextrins in high selectivity to give crystalline compounds. β‐Cyclodextrin forms complexes with poly(dimethylsilane)s of low molecular weight only, γ‐cyclodextrin with poly(dimethylsilane)s of high molecular weight in high yield, and α‐cyclodextrin does not form complexes with poly(dimethylsilane) at all. Complexes were isolated and characterized by spectroscopic methods and X‐ray diffraction.     

Supported Noble Metal Catalysts and Adsorbents with Soft Lewis Acid Functions

Heterogeneous noble metal catalysts exhibit various functions. Although their redox functions have been extensively studied, we focused on their soft Lewis acid functions. Supported Au, Pt, and Pd catalysts electrophilically attack the π-electrons of soft bases such as alkynes, alkenes, and aromatic compounds to perform addition and substitution reactions. Hydroamination, intramolecular cyclization of alkynyl carboxylic acids, isomerization of allylic esters, vinyl exchange reactions, Wacker oxidation, and oxidative homocoupling of aromatics are introduced based on a discussion of the active species and reaction mechanisms. Furthermore, the adsorption of sulfur compounds, which are soft bases, onto the supported AuNPs is discussed. The adsorption and removal of 1,3-dimethyltrisulfane (DMTS), which is the compound responsible for the stale odor of “hine-ka” in alcoholic beverages, particularly Japanese sake, is described.