Comparative molecular field analysis (CoMFA) has been widely used in 3D QSAR studies. Although CoMFA is a general method, there are some critical problems in the practical usage. A major problem of CoMFA and most other 3D QSAR methodologies is that the results are dependent on the chosen bioactive conformations and the corresponding alignment rules of molecules. Recently, we have proposed a novel method with a 3-way PLS formulation for solving the conformation/alignment problem [K.Hasegawa, M.Arakawa and K.Funatsu, Chemometrics Intell. Lab. Syst., 50, 253-261 (2000)]. In this study, we extended the previous method to investigate conformation and alignment independently. The possible 3D conformations of all molecules were generated by conformational analysis and they were characterized by field variables of CoMFA. Then 4way array for 4way PLS analysis was created by similarity criterion, and conformations largely contributing to inhibitory activity were selected. To demonstrate the general utility, the data set of glucose analogue inhibitors of glycogen phosphorylase was used as a test sample.

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Comparative molecular field analysis (CoMFA) has been widely used in 3D QSAR studies. Although CoMFA is a general method, there are some critical problems in the practical usage. A major problem of CoMFA and most other 3D QSAR methodologies is that the results are dependent on the chosen bioactive conformations and the corresponding alignment rules of molecules. Recently, we have proposed a novel method with a 3-way PLS formulation for solving the conformation/alignment problem [K.Hasegawa, M.Arakawa and K.Funatsu, Chemometrics Intell. Lab. Syst., 50, 253-261 (2000)]. In this study, we extended the previous method to investigate conformation and alignment independently. The possible 3D conformations of all molecules were generated by conformational analysis and they were characterized by field variables of CoMFA. Then 4way array for 4way PLS analysis was created by similarity criterion, and conformations largely contributing to inhibitory activity were selected. To demonstrate the general utility, the data set of Benzodiazepine analogue inhibitors of Cholecystokinin was used as a test sample. Furthermore, validation using external data was carried out to prove the usefulness of selection method of conformations and alignment rules by 4wayPLS method proposed in this study.

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If the structures of proteins are modeled by hard balls representing each alpha-carbon atom then the maximum overlapped volume of those balls provides a measure of the degree of similarity between a pair of proteins. This paper describes the use of a genetic algorithm (GA) to calculate such similarity measures, with experiments being carried out that matched individual protein structures both against themselves and against other proteins. These experiments demonstrated that the best results were obtained by parameterising the GA as follows: using an exponential distance measure with a coefficient value of -0.1 as the fitness function in a steady-state GA with 100 chromosomes, a selection pressure of 1.5 and a crossover probability of 40%. The resulting similarities are highly correlated with those resulting from the allover method for calculating inter-protein similarities.

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The quantitative description of chemical structures and their activities is called quantitative structure-activity relationships (QSAR). Recently, Comparative Molecular Field Analysis (CoMFA) is more often used. In the CoMFA modeling, steric and electrostatic interaction energies between molecules and probe atoms are used for the modeling. And the relationship between these interaction energies and biological activities are modeled using partial least squares (PLS) method. Therefore, three-dimensional structural features of the molecules can be directly reflected to the CoMFA model. However, conventional CoMFA have some problems; for example, because of the CoMFA model has a large number of descriptor variables, the model would become unstable. If advantages are mentioned, it is possible to model efficiently. In this study, we developed a new 3D-QSAR method. We have analyzed relationship between each Molecular electrostatic potential (MEP) on the van der Waals surface and their activities on 25 Molecules that are various substituted salicylamides, having 2-pyrrolidinylmethyl side chains. The compounds belong to the class of substituted benzamides and display potent binding to the dopamine D-2 receptor. MEP is important information for studies on pharmacologinal activity. The three-dimensional of the MEP is largely responsible for binding of ligand molecule at the active site of receptor. First each molecular three Cartesian coordinates of points on its van der Waals surface and MEP values of those points are obtained, and train Kohonen neural network with its three Cartesian coordinates. Then two-dimensional maps of MEP for 25 molecules are obtained. The characteristic of molecule surface is able to be expressed well by Kohonen network. Then they are analyzed by PLS method or 3wayPLS method. The result suggested that 3wayPLS method could show the effective regions for activity more clearly than 2wayPLS method did. Last all data was divided into training data and test data by D-optimal designs and test data were predicted. The prediction result suggested that 3wayPLS method is better than 2wayPLS method too.

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In the field of chemometrics, statistical methods such as partial least squares regression (PLS), principal component analysis (PCA) have been applied to establish chemical model, then the model are applied to material design. However in the case of the conventional methods, it is difficult to find a set of the independent variables that satisfies several properties at the same time. Therefore in this study we developed a reverse analysis program that solves the problem.

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Fluorination mechanism of 2-hydroxyl-3-phenylcarboxylate with diethylaminosulfur trifluoride (DAST) was investigated by using ab initio MO calculations. This reaction gave two products, 2-fluoro-3-phenylpropiolate and 2-fluoro-3-phenylpropionate, depending on the substituent on the phenyl ring (NO2, H, OCH3). Therefore, two possible mechanisms, the SN2 mechanism and that via the phenonium intermediate, were examined. As the activation energies for the SN2 reaction of the three compounds are almost same each other and very low, the substituent effects on the phenyl ring is too small to distinguish the product distribution observed for the compounds. The stabilization energy of phenonium ions, which are feasible intermediates for the SN1 reaction, are large difference between the three intermediates. As a result, the fluorination is considered to be proceeded on SN1 mechanism. Additionally, it is shown that the ability of leaving group for an intermediate generated from the reaction of alcohol with DAST is as large as mesyl and tosyl groups.

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Rhodopseudomonas viridis (Rps. viridis) is a bacterial photosynthetic reaction center (PRC) and a huge molecular system. On the basis of information on heavy atoms (C, N, O, Mg, S, and Fe) from Protein Data Bank of Brookhaven National Lab., we constructed the molecular structure, and released the Cartesian coordinates from home page (URL=http://www.nimc.go.jp/cicsj/jcac/kao1/prc.txt). We confirmed that Rps. viridis was 20,479 atoms including 201 water molecules, and the total charge was -7. Because the previous studies have reported different information on this system, we think this article is a basic data to investigate photo induced electron transfer at the PRC.

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In dye-sensitized solar cells, the electron transfers from the excited state of the dye molecules to the conduction band of the semiconductor with a high efficiency. We have investigated the mechanism of the ultra fast ET using char-ge equilibration (QEq) method and the generalization for charge separation systems (QEq-CS). On the basis of our calculations, we discuss the importance of the covalent bonding between the dye molecule and the semiconductor sur-face. The change of partial atomic charges indicates that the injected electron locates on some region beneath the donor group of the dye molecule rather than around the Ti atom binding the dye molecule This result explains that the cova-lent bonding keeps the close distance between the donor and acceptor to achieve ultra fast ET process.

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Isosurfaces (surfaces having identical function values) of a hydrogen atomic orbital are drawn at various scales using the software called AVS (Application Visualization System). The authoring software QTVR (QuickTime Virtual Reality Authoring Studio) enables us to see a moving picture of an orbital from an overview in a large region to a detailed view in a small region. This technique was effective to look into an inner structure of the atomic orbital which are hidden by an outer isosurface. Examples of representation of 2s or 5d(3z2-r2) atomic orbital are given.

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With the progress of genome projects, a vast amount of nucleotide sequence data is now available, which makes it possible to study the species-specific gene expression systems involving transcription and translation for a wide range of organisms. To understand species-specific translation system, it is important for comprehending the whole set of tRNAs for individual species. In the present study, we have developed a procedure for detecting tRNAs in DNA sequences based on the tRNA cloverleaf structures, and estimating the whole numbers of isoaccepting tRNAs in multicellular species Caenorhabditis elegans and Drosophila melanogaster whose genome sequences are nearly determined.

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In proteomics and proteome analysis using 2-dimensional electrophoresis (2-DE), molecular weights and N-terminal sequences for individual protein spots are relatively easily determined. In the present study, we propose a procedure for estimating fragmentation process of a protein based on the inclusion relation among peptide sequence, and estimate fragmentation process of vitellogenin (Vtg) of Oncorhynchus masou based on N-terminal sequences and molecular weights for 48 fragments, that appear at very high concentrations in the whole embryos of O. masou. A potential proteolytic process of Vtg is discussed in relation to normal and abnormal developmental embryos.

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It has been possible to use the computer-assisted synthesis design system such as AIPHOS and EROS in order to create new synthetic routes of target compounds. However, these systems produce several synthetic routes without giving information which route should be applied first in experiments. It is common knowledge that transition states are keys for how to estimate easiness of chemical reactions and computational chemistry delivers that answer. However, organic chemists have to take great effort to use molecular orbital calculations and to obtain transition state geometry. A system, which makes it possible to treat transition states even by organic chemists, should be very useful. In the present study, we intended to develop a new program which offers organic chemists to search transition states easily and to analyze chemical reactions in detail. The system includes three standard methods, which are the minimum energy path, the saddle and the contour methods. The program was also installed the substitution method, which adds a cyclic or an acyclic substituent to transition state structures previously obtained. It was confirmed that this method is very useful to find transition states of chemical reactions.

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