One of the most important areas for the application of genomic science and technology is said to be personalized medicine (which is often called tailor-made medicine in Japan). Personalized medicine is an idealized medical practice aiming to give the right drugs to the right patients at the right times. It has been widely admitted that many projects for finding Single nucleotide polymorphisms (SNPs) are the basis for such practice. However, such knowledge alone is by no means sufficient, for good practice must be supported by well trained medical professionals who can easily access a wide range of relevant data and knowledge at their clinical sites. New informatics are also needed in order to utilize these data and knowledge effectively. Such an informational environment, I.e., data and knowledge bases and computational tools, would be called the infrastructure for personalized medicine. The infrastructure would also be useful in pharmaceutical research for finding leads and analyzing detailed mechanisms of drug actions. As the only national institution for pharmaceutical research in Japan, we have started to implement some components of the infrastructure and put their prototypes on the Web. Further research initiatives are being discussed in the Chem-Bio Informatics Society as components of its Grand Challenge Projects.

View full abstract

A database comprising about 1, 500 drugs clinically used in Japan has been constructed aiming to mine the information regarding essential chemical characteristics suitable for drugs. The ring systems and functional groups observed in drugs have been extracted and compiled into a part of the database. Although the relevant information is relatively biased, it would assist drug designers in the selection of chemical scaffolds and functional groups.

View full abstract

Three-dimensional models of the gelatinase catalytic domains were built from collagenase structures by the homology modeling technique. The docking of different types of inhibitors was then studied in an attempt to obtain structural insight into their binding modes. In the case of an amide compound docked with gelatinase A, almost the same binding mode was obtained as that observed in the crystal structure of another amide compound complexed with collagenase. With respect to our series of matlystatin analogs, the key hydrogen bonding and hydrophobic interactions with gelatinase B were similar to those of the above amide compounds, although these derivatives have a unique piperazine ring. The length and hydrophobic nature of the S1' subsite was well consistent with the observation that the inhibitory activity rises as the alkyl chain at P1' becomes longer. The binding mode of a sulfonamide inhibitor was slightly different from that of amide and piperazine inhibitors, but similar to that proposed recently for another sulfonamide inhibitor.

View full abstract

We propose a new charge equilibration approach that depends upon molecular 3D structure. Nishimoto - Mataga equation is used to express the shielding effect. With the present approach, it is not necessary to iterate simultaneous equations for evaluating charge equilibration, although that is required in the Qeq method. Atomic charge calculations were carried out for several organic molecules. Calculated charge distributions are in good agreement with experimental values.

View full abstract

cDNA microarrays are very convenient tools that can be used to understand changes in genome-wide patterns of gene expression. The yeast DNA microarray contains 5880 ORF cDNA probes, which is almost whole genome, on a glass slide. We analyzed genome-wide transcript profiles following exposure to Cadmium (Cd) or Mercury (Hg) with the yeast DNA microarray, and while 22 genes were induced by both heavy metals, there were many discrepancies in those profiles. From these results, we concluded that yeast microarrays are valuable for bioassay of environmental agents.

View full abstract

The reaction of transmethylation plays an important role in the immune system. Some kinds of sulfonium compounds, which have a labile methyl group, are considered to become the supply source for methyl groups in biological systems. We examined the physicochemical properties of sulfonium compounds from the point of structure activity relationships analysis in order to develop an antiallergy drug. We found that several sulfonium compounds have immunological activity, and 2-hydroxyethyldimethylsulfonium p-toluenesulfonate (4) was chosen as the lead compound for further studies.

View full abstract