We have implemented an efficient, user-friendly, and web-based "biosimulator" named called BEST-KIT (Biochemical Engineering System analyzing Tool-KIT: http://helios.brs.Kyushu -u.ac.jp/˜bestkit/) for analyzing a a large scalelarge scale nonlinear reaction networks such as metabolic pathways. The BEST-KIT consists mainly consists of two kinds of modules, "MassAction" and "EnzymeKinetics.". In this study, we have developed a new module, "MassAction++, ", which can construct and analyze reaction schemes represented by both mass action law (mass balance) and approximated velocity functions of enzyme kinetics at steady state. All modules in BEST-KIT are developed in Java applet style, and can be carried outrun on the "any" platform machine through the web browser. The "MassAction++" module was developed by in Java applet style. andIt can save data related on to the constructed reaction scheme and time course data onto the client disk space and can load it onto the web browser.

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We evaluated the effects of dimethyl sulfoxide (DMSO) on yeast cells by taking advantage of DNA microarrays and bioinformatics tools such as cluster analysis. There were 147 induced and 246 repressed genes in the expression profiles of 5, 535 yeast genes by DNA microarray analysis. From the comparison of these expression profile changes in response to DMSO treatment with other publicly available expression data, the gene expression pattern of DMSO treatment resembled those of DTT and diamide. This suggests that DMSO causes damage similar to that caused by DTT and diamide. Further, DMSO inhibits protein folding and processing in the endoplasmic reticulum (ER), cell wall damage can result from the formation of improper disulfide bonds in the ER. The genes expressed during the DMSO treatment were also grouped in the cluster including the nonfermentable carbon sources, such as ethanol and galactose, during the stationary phase. This suggests that DMSO induces glucose depletion or starvation in yeast cells accompanied by new energy synthesis via an unknown metabolic pathway that utilizes DMSO as a carbon source.

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The three dimensional structure of a pheromone binding protein from Bombyx mori complexed with its substrate was determined recently [Sandler et al., Chem. Biol. 7, 143-151 (2000)]. The structure suggested that a loop formed by amino acid residues 60-69 could serve as a flexible lid into the pheromone binding pocket. To examine the above hypothesis, a molecular dynamics simulation was performed for a substrate free form of the protein starting from the crystal structure. In the simulation loop 60-69 took a conformation different from that in the substrate bound form. Also, the loop was the most flexible region of the protein. Thus, the simulation supports the hypothesis that the loop is a flexible lid.

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