Plaque Structure, Prevention and Possible Cure of Alzheimer’s Disease: An Exploratory First Principle Molecular Computational Study

A model of ABeta-sheet in Alzheimer’s disease (AD) and fragments of glutathione (GSH) as a possible AD related antioxidant were studied. Conformational optimizations were performed using a three strand trialanine Beta-pleated sheet as a model of the ABeta-sheet. Two fragments of GSH: Gamma-glutamylmethylamide and N-acetyl-cysteine glycine (N-ACG) were optimized to find their conformational spaces. Calculations were performed using the restricted Hartree-Fock (RHF) formalism with a 3-21 contracted Gaussian (3-21G) basis set (RHF/3-21G level of theory). All conformational studies were carried out from first principles of quantum mechanical computations using the Gaussian 98 (G98) program. On the basis of computed fragment geometries, the initial conformation of the neutral antioxidant glutathione (GSH) was predicted for the future studies. From the study of hydrogen bonding structure of amyloid modeled by three strand trialanine Beta-pleated sheet, a hypothetic peptido-memetic drug was suggested to break ABeta-sheet structure of amyloid in the brain of AD patients.