Obtaining three-dimensional coordinate of chemical substrates from its structural formula is a crucial process in drug design. We here discuss existing methodology and programs, and compare them with a method we developed. Our method is based on a simplified distance geometry algorithm followed by force field optimization. Repetitive generation of structure provides fairly stable conformer in reasonable timescale even for molecules with rather flexible ring systems. Validation of structures was made by flexible fitting with CSD X-ray structure. More than 80% of five thousands converted geometries are found within less than 0.3 angstrom RMSD from the experimental structures.

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We investigated new integration technology and developed a computational environment, called the “virtual experiments system”. The virtual experiment system consists of the integration of various technologies for materials design. A special feature of a virtual experiment system is introduction of a new concept “taskflow” to integrate those various elements of computational technologies technology such as simulation, database, knowledge information processing, visualization and the human interface. The virtual experiments system supports a chain of workflow for materials design due to apply the “taskflow”. The virtual experiments system is available to use via network, because the system is implemented based on web technology. In order to evaluate the investigated integration technology and the virtual experiments system, we applied the virtual experiments system to design superalloy.

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Structures of reaction intermediate that appeared in the monooxygenation reaction cycle by cytochrome P-450 were determined by density functional theory method. Model structures for the calculation were constructed by extracting heme and 5th and 6th ligands of the heme from X-ray crystallographic structure registered in the Protein Data Bank (PDB). Stable structure of oxy-ferrous hemerevealed that there was no bond cleavage of an oxygen molecule at the 6th ligand in reduction by a single electron. The negative charge of the 6th ligand was reduced to only -0.32 e. Subsequently, a ultimate species for the monooxygenation reaction by P-450, which was proposed in the previous paper [3], was produced in the 6th ligand of heme. The stable structure revealed that no O-O bond cleavage occurred, though distance of the 0-0 bond of the 6th ligand increased from that of the oxy ferrous heme. The total charge of the 6th ligand was approximately neutral. A set of structural changes of the 6th ligand of heme in the reaction process until the production of the ultimate active species by the introduction of two electrons and the binding of two protons was the same as those of the 6th ligand alone. For this reason, we concluded that the monooxygenation reaction mechanism by P-450 might be the reaction between the 6th ligand of heme and the substrate. The role of heme in themonooxygenation reaction mechanism by P-450 might be to transfer electrical charge to the bindingoxygen of the 6th ligand, keeping interaction between an oxygen atom that is not directly binding with heme Fe atom and the oxygenating site of the substrate.

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Boron isotope separation factors, which are calculated from boron isotope reduced partition function ratios, were estimated by ab initio molecular orbital calculations. The geometries of B (OH) ₃, B (OH) ₄^-, andtriethanolamine borate (TEA-B) were optimized and then the normal frequencies were calculated for each boronisotopes using eight kinds of the methods and ten kinds of the basis sets. The boron isotope separation factor wasabout 1.03 for both B (OH) ₃ - B (OH) ₄^- system and B (OH) ₃ -TEA-B system.

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Vibrational frequencies and infrared intensities of dichloromethane CH2Cl2 molecule in the liquid phase have been calculated with the ab initio molecular orbital method using many combinations of basis set functions, electron correlation correction methods, and solvent effect correction methods, and compared with experimental values. Recommended combination of computational methods was proposed for frequency, but infrared intensity could not be reproduced.

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In order to elucidate the effect of solvent structure on the formation of oxidation active species over TS-1, the stability of Ti-H₂O₂-solvent clusters, which are expected to be the precursor of oxidation active species, was estimated by means of the density functional theory calculation. The order of the stability, Ti-H₂0₂- CH₃OH>Ti-H₂O₂-C₂H₅OH>Ti-H₂O₂-C₃H₇OH, was in agreement with that of the yield of hydroquinone and catechol for 3h in these solvent, 20.2% (CH₃OH)>6.3% (C₂H₅OH)>1.4% (C₃H₇OH). These results suggest that the co-adsorbed solvent affects the stability of H₂O₂ adsorption on Ti, and consequently determines the reaction rate.

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Mechanism of catalyzed oxidation reaction of p-cresol by HRP compound II was analyzed using AM 1-d semiempirical molecular orbital calculation method on the basis of X-ray crystallography structure. Arg-38 residue was proved to decrease activation energy of this reaction (9.575kcal/mol).

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Molecular visualization package using Mathematica is developed. We describe the detail of the molecular visualization algorithm, the structure of the package, the molecular visualization method specifying atomic positions, the incorporating method of numerical data file, and saving procedure of the graphics in optional format. Fully executable source codes for Mathematica are presented.

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Visualization of the numerical simulation is useful for understanding of physical phenomenon or chemical reaction. For example, graphical representation of the lines of electric force and the isosurfaces, which are calculated by the electrostatic potential around a molecule, with molecular structure brings you easier analysis and prediction about molecular properties. However, if you didn't have enough skills, it would be difficult to read these natures from the printing or the display, which originally are three-dimensional information. So, in this paper, we propose the new tool based on virtual reality technology, it is able to use for intuitive understanding. A main purpose of this system is to feel the Coulomb force around the molecule directly. Not only you can observe molecular properties three-dimensionally, but also you can feel the force from the electric field actually. The general personal computer, the stereoscopic device and the force display device on the market compose it. User is able to get interesting experiences by interactive operation.

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