Effect of D23N mutation on the dimer conformation of amyloid ß-proteins: ab initio molecular simulations in water.

The molecular pathogenesis of Alzheimer's disease (AD) is deeply involved in aggregations of amyloid ß-proteins (Aß) in a diseased brain. The recent experimental studies indicated that the mutation of Asp23 by Asn (D23N) within the coding sequence of Aß increases the risk for the pathogeny of cerebral amyloid angiopathy and early-onset familial ADs. Fibrils of the D23N mutated Aßs can form both parallel and antiparallel structures, and the parallel one is considered to be associated with the pathogeny. However, the structure and the aggregation mechanism of the mutated Aß fibrils are not elucidated at atomic and electronic levels. We here investigated solvated structures of the two types of Aß dimers, each of which is composed of the wild-type or the D23N mutated Aß, using classical molecular mechanics and ab initio fragment molecular orbital (FMO) methods, in order to reveal the effect of the D23N mutation on the structure of Aß dimer as well as the specific interactions between the Aß monomers. The results elucidate that the effect of the D23N mutation is significant for the parallel structure of Aß dimer and that the solvating water molecules around the Aß dimer have significant contribution to the stability of Aß dimer.

Industry meets theory: computational R & D for innovative products.

We introduce our activities for applications of first-principles theoretical calculations to various research and development processes for innovative electronic products. We present our recent selected results for four kinds of materials, which are the rare-earth element doped ceramic dielectric material BaTiO(3), BaTiO(3) ceramic nanoclusters and alkali-metal Li storage materials, i.e., graphite and sulfide Li(x)FeS(2).

Density functional theory investigation of benzenethiol adsorption on Au(111).

We have studied the adsorption of benzenethiol molecules on the Au(111) surface by using first principles total energy calculations. A single thiolate molecule is adsorbed at the bridge site slightly shifted toward the fcc-hollow site, and is tilted by 61 degrees from the surface normal. As for the self-assembled monolayer (SAM) structures, the (2 square root of 3 x square root of 3)R30 degrees herringbone structure is stabilized against the (square root 3 x square root 3)R30 degrees structure by large steric relaxation. In the most stable (2 square root 3 x square root 3)R30 degrees SAM structure, the molecule is adsorbed at the bridge site with the tilting angle of 21 degrees, which is much smaller compared with the single molecule adsorption. The van der Waals interaction plays an important role in forming the SAM structure. The adsorption of benzenethiolates induces the repulsive interaction between surface Au atoms, which facilitates the formation of surface Au vacancy.

Tail molecule dependence of thiolate adsorption on Au(111) surface: Theoretical study.

The adsorption of thiolates with various tail molecules on the Au(111) surface has been investigated by first-principles calculations. We have considered six typical thiolate molecules, that is, methylthiolate, ethylthiolate, ethylenethiolate, acetylenethiolate, benzenethiolate, and thiophenethiolate. It is found that these thiolates exhibit little difference in their stable adsorption geometries. They are adsorbed at the bridge site with being significantly tilted from the surface normal. The adsorption energy of thiolate on Au, on the other hand, largely varies depending on the type of tail molecule, and is linearly proportional to the binding energy of thiolate with H. We discuss the tail molecule dependence in terms of the bonding environment around the C atom connected to the head S atom.