Many-core processors such as graphics processing units attract attention as the high-performance computational devices. Architectural development of computers over thirty years is briefly reviewed. Because of the breakdown of the CMOS scaling law, accumulation of simple CPU cores on a chip, called as many-core processors, becomes a rational way to achieve performance improvement. It is pointed out that not the absolute performance but the performance per watt matters near future. Next the most famous many-core processor, NVIDIA's FERMI, is introduced. It is a massively parallel processor,and is suitable for compute intensive, highly parallel, yet simple tasks. Several attempts to accelerate the computer simulations by using the GPU are reviewed, including the molecular dynamics simulations, first-principle calculation with plain wave basis set, and the quantum chemical calculations.

View full abstract

The detail of the potential profile of the electrical double layer at the solid/liquid interface is usually not discussed because the potential difference between the electrode and the bulk solution has great significance for the redox reaction and the charging of the electrode. In the case of the self-assembled monolayer of thiols with dissociative group terminals on Au(111) surface the charge density has a high value such as 0.74μC m-2. For this interface we found that the reaction rate of the redox species such as [Fe(CN)6 ]3-/4- in electrolyte solution is enhanced by the order of more than 105 even when the coverage of the dissociated terminals of ammonium group terminal is less than 1/100. By the use of the primitive model and the canonical Monte Carlo simulation the three-dimensional distribution of the potential was evaluated. With the combination of the Butler-Volmer-Frumkin theory and the potential profiles the reaction rate was numerically calculated. The calculated change in the reaction rate was in good agreement with the experimental results. From this theoretical analysis we had the conclusion that the enhancement of the redox reaction rate can be induced by the local electrical double layer effect around the dissociated group terminal.

View full abstract

The objective of this study is to construct a model which can predict results of reverse mutation test with high accuracy. For this end, we propose a novel ensemble modeling method in which a lot of support vector machine (SVM) models are constructed as a sub-model and integrated to predict mutagenicity. For constructing sub-models, a part of data matrix which is randomly selected from an original data matrix and randomly determined SVM parameters are used. After the construction of sub-models, a certain number of models which have high accuracy rate are selected and integrated to predict mutagenicity. We constructed an ensemble model using a data set of reverse mutation test which was collected by Hansen et al. [K. Hansen, et al., J. Chem. Inf. Model., 49, 2077-2081] to estimate the proposed method. As a result, the ensemble model with accuracy of 79.6% was successfully obtained. The area under ROC-curve (AUC) is 0.866, which is slightly better than that of Hansen et al. Thus we concluded that the ensemble modeling with SVM sub-models are a promising method for predicting mutagenicity of organic molecules.

View full abstract

A membrane bioreactor (MBR) is the equipment to filtrate sewage or factory disposal water by MF/UF membrane. Activated sludge is used to remove organic substances metabolically and filtrated to membrane by transmembrane pressure (TMP). Though MBR is able to remove activated sludge, other particles of raw water, or both of them effectively, increase of TMP as a result of fouling growth brought by deposition of particles is one of the biggest problems for improving its performance. Membrane needs to be washed when TMP reaches about 25-30 kPa. The focus of this study is to estimate TMP with statistical prediction models and also know when the membrane wash-up will become necessary for the realization of distributed MBR and its unattended operation. In this study, two statistical models were constructed between explanatory variables related to fouling and an objective variable, i.e., membrane resistance (R) or deposition rate of foulant (DR). It is able to predict TMP because R or DR could be converted into TMP. As results of TMP prediction with real industrial data, usage of DR as an objective variable improved the accuracy of TMP prediction.

View full abstract

The first stage of research for the development of new drugs is a promising lead compound discovery; its efficiency has been advanced. The Problem of the virtual library for virtual screening in drug discovery is to achieve both scale and diversity. Even if lead compounds will be found as a high score, because they are virtual compounds, the study of their synthesis will require a significant cost. To solve these problems, we have studied the use of the transform has been described structural changes and environmental changes at the reactive site that is extracted from the database. And we have developed a system for building a virtual library containing information about the synthetic pathway. This system can propose the precursors for the synthesis of the target, and manages them as reaction schemes. The tree for synthesis pathway is formed by repeating that the structure of the output re-enter. So the synthetic route to lead compounds from each compound in the virtual library is obtained by tracing the synthetic pathway on the tree. In addition, this system has the possibility of the cost evaluation of two or more synthetic routes to the lead compounds.

View full abstract

Quantum chemical calculation is one of the most powerful tools to investigate chemical phenomena. Although remarkable advances on hard and soft wear for the theoretical calculations has been progressing for last ten years, there still exist many problems to be solved for chemists, i.e., setting good environments for calculations and having good skills to deal with calculated results. Data Base on Results of Quantum Chemical Calculations (DBRQC) should be useful for chemists who cannot access environments for the theoretical calculations. We are now constructing a data base named DBRQC which include (1) key words of calculations (2) Cartesian coordinates of optimized structures, (3) descriptions of data using Molecule Description Languages such as Smiles, InChI (4) Mol files, (5) 2D structure of molecule, (6) output of the Gaussian03 program. The data base include 480 data, mainly results at the B3LYP/6-31G(d) level of theory. DBRQC can be accessed via Internet since PostgreSQL and a scripting language, php, are used to construct it. After searching data based on key words, Smiles or InChI, downloads of desired data are possible.

View full abstract

The solvent effect on the reaction has been studied using experiments and theoretical computations. However, it is known that the behavior of the solvent is statistically observed in experiments, and it is difficult to theoretically analyze their behavior. Our laboratory has been developed QM/MC/FEP method that evaluats solvent effects on chemical reactions. The method make it possible to produced theoretical values consistant with experimental ones. In this study, thermodynamic parameters from theoretical calculation are compared to ones from experiment works to analyze solvent effects on Prilezhaev Reaction in detail.

View full abstract

Conformational search program CONFLEX can quickly find the chemically significant conformers of large and flexible molecules. However, as the number of conformers increase, network topology in conformational space that consists of the interconversion relationships between conformers is more complex. To analyze and understand the dynamic behaviors of such molecules with conformational exchanges, development of visualization technique for conformational topology is quit important. In this paper, we propose a visualization technique by multiple spherical representations of conformational space and topology: whole conformational space is represented by one central large sphere and a conformation is drawn as a point or a small sphere on the central sphere. If there are a large number of conformations, all conformations are classified by several conformational clusters and each cluster can be represented by a middle size of sphere (like a moon) having a partial conformational topology. In this study, accuracy and qualitative evaluation for our visualization technique of conformational topology have been examined in comparison with general 2D and 3D representations for well-known conformational topologies of cyclohexane, cycloheptane and cyclooctane. New supporting tool for exploring the transition state structure coupled to both this visualization system and CONFLEX will be also discussed.

View full abstract

We study the effect of chemical composition in copolymers of ethylene and higher α-olefins, butene-1 (PEB), hexene-1 (PEH), octene-1 (PEO) and decene-1 (PED) on the structural, conformational and thermodynamic properties of their melts. To this end, we perform extensive simulations using a connectivity altering Monte Carlo method extended to short chain branched copolymers. Good equilibration of the systems considered (melts of long chains containing on average 1000 carbon atoms in the backbone and up to 20-40 mol% of α-olefin) has been achieved. The calculated values of radii of gyration, <S2>, plotted against the weight fraction of side chains, fb, fall approximately on a single curve, in agreement with experiment based correlations. The observed reduction of chain dimensions is due to an increase in the population of gauche conformational states along the backbones. Other properties, such as cohesive energies and primitive paths from topological analyses of melts also form common curves when plotted with respect to fb. Molecular mechanisms underlying the observed evolution in structural and thermodynamic properties will be discussed.

View full abstract

The combination method between asymmetric Kekule structures (CMAK) was expanded to the structure prediction of acenes and phenylenes seriese. The predicted structures by the CMAK correspond to those calculated ab initio CASSSCF and CCSD(T) MO and B3LYP density functional methods. The CMAK can characterize the structures. The aromaticity for whole ring and each ring in the treated compounds was estimated by the index of deviation from aromaticity (IDA), was proposed by us in the previous. The estimated aromaticity corresponds fairly to the characterization of the structure predicted by the CMAK. The predicted structures of linear acenes indicate the aromaticity of the central ring and also explain the reactivity for the central ring from the characterized aromaticity. For [n]phenacenes, the side ring in the compompounds indicates much aromaticity. From the position of the much aromaticity for linear acenes and [n]phenacenes, the difference of the reactivity for these compounds can be explained. For the isomers of benzo[1,2:4,5]dicyclobutene and benzo[1.2:5,6]dicyclobutene, the critical difference of the structure and the aromaticity for the central six-membered-ring was explained.

View full abstract

A helix structure is one of the important building components of proteins. In this study, we focus on the screw-sense reversal process between the right- and left-handed alpha-helices. We calculated the phi-psi map of alanine model molecule by optimizing all other geometrical parameters. Based on the phi-psi map, we found four TS structures, which might be related to reversal pathways. We performed direct ab initio MD simulations from each of those TS structures and found two appropriate routes. In addition, we calculated the energy of 10-mer alanine model to estimate the required number of amino acid residues for the reversal. We found that the reversal pathway of right-handed alpha helix to left-handed alpha helix might proceed via beta region and 2 amino acid residues are necessary for the reversal.

View full abstract

Soft sensors have been widely used in industrial plants to estimate process variables that are difficult to measure online. Soft sensor models predicting an objective variable should be constructed with only important explanatory variables in terms of predictive ability, better interpretation of models and lower measurement costs. Besides, some process variables can affect an objective variable with time-delays. In some studies, soft sensor models are constructed using process dynamics and in others, the selection of process variables is used to increase the predictive accuracy. No one, however, has yet realized the optimization of both considerations in process dynamics and process variable selection. We therefore have proposed the methods for selecting important process variables and optimal time-delays of each variable simultaneously, by modifying the wavelength selection methods in spectrum analysis such as stacked partial least squares (PLS), searching combination moving window PLS, and genetic algorithm-based wavelength selection. The proposed methods can select time-regions of process variables as a unit by using process data that includes process variables that are delayed for a duration ranging from 0 through some time. The case study with real industrial data confirmed that predictive, easy-to-interpret, and appropriate models were constructed using the proposed methods.

View full abstract

Distillation is one of the dominating separation processes, but there are some problems that inseparable mixtures are formed in some cases. This phenomenon is called as azeotropy. It is essential to understand azeotropy in any distillation processes since azeotropes, i.e. inseparable mixtures, cannot be separated by ordinary distillation. In this study, to construct a model which predicts the azeotropic formation at any pressure, a novel approach is presented with support vector machine (SVM). The SVM method is used to classify data in the two classes, that is, azeotropes and nonazeotropes. 13 variables including pressure data were used as explanatory variables. From the result of comparing the SVM models which were constructed with data measured at 1atm and data measured at any pressure, the 1atm model shows a higher prediction performance to the data measured at 1atm than the any pressure model. Thus, for improving the performance of the any pressure model, we focused on intermolecular forces of solvents. The SVM models were constructed with only data of the solvents having same subgroups. The accuracy of the model increased and it is expected that this proposed method will be used to predict azeotropic formation at any pressure with high accuracy.

View full abstract

Soft sensors are widely used to realize highly efficient operation in chemical process because every important variable such as product quality is not measured online. By using soft sensors, such a difficult-to-measure variable y can be estimated with other process variables which are measured online. For estimating y without degradation of a soft sensor model, a time difference (TD) model was developed previously. Though a TD model has high predictive ability, it does not function well when a process is operated under conditions that have never been observed. In order to cope with this problem, a soft sensor model can be updated with newest data. But, updating a model needs time and effort for plant operators. We therefore developed an online monitoring system to judge whether a TD model can predict y accurately or an updating model should be used for both reducing maintenance cost and improving predictive accuracy of soft sensors. The monitoring system is based on a support vector machine or standard deviation of y-values estimated from various intervals of time difference. We confirmed that the proposed system has functioned successfully in a distillation column with real industrial data.

View full abstract

Lipase A from Bacillus subtilis 168 (LipA) shows enantioselectivity on ester hydrolysis reactions producing (R)-IPG (1,2-O-isopropylidene-sn-glycerol) more than (S)-IPG from the racemate. In order to investigate the reaction mechanism, we estimated interaction energy between residues in LipA and the substrate-Ser77 complex by using Gamess/FMO method. Then, selecting five residues playing important role on the hydrolysis reaction, the energies of three states of Michaelis Complexes (MC), Transition States (TS), and Tetrahedral Intermediates (TI) for two crystals of 1R50 (producing (R)-IPG) and 1R4Z (producing (S)-IPG) were calculated with MOPAC PM6. The initial stage of the possible hydrolysis mechanism has become to be clarified qualitatively.

View full abstract

Casein kinase II (CK2), a serine-threonine protein kinase, is distributed ubiquitously in human body. It exists as a tetramer composed of two catalytic subunits (α and α') and two control subunits (β). Amino acid sequence homology between the catalytic subunit α and α' is very high, 83%. Inhibitors of this enzyme have been explored for cancer, virus infection and glomerulonephritis therapies, and several highly potent compounds have been reported as ATP competitive inhibitors. On the other hand, hematein, a natural compound isolated from Caesalpinia sappan, inhibits CK2α in an ATP uncompetitive manner, whereas it inhibits CK2α' in a competitive manner. We have investigated the binding mode of hematein to both isozymes using docking studies followed by the binding energy analysis with the MM/PBSA method and the simulated annealing simulation. The results suggested that hematein could bind to the ATP binding site of the both isozymes. In addition, it might bind to the allosteric site and the substrate binding site of CK2α.

View full abstract

We reported that simple alkyl- and arylpyrazines were showed the 50% inhibitory concentration towards arachidonic acid-induced and collagen-induced aggregation of rabbit blood platelet in vitro. Among the 48 pyrazine derivatives, 2,3-bis(p-methoxyphenyl)pyrazines showed the most potent inhibitory activity. Therefore, molecular docking was carried out using the ASEDock module in the MOE. As results of the ASEDock, among the three interaction energies, the van der Waals interaction energies were contributed to the stability of receptor-ligand complexes. The Docking structures suggested the interaction between phenyl groups at 2,3 position and TYR385 and PHE518 and between the substituents at 5,6-position and ARG120. In order to clearly the interaction of the COX-ligands, the InterFragment Interaction Energy (IFIE) analtsis was calculated by Fragment Molecular Orbital method. Consequently, the most strongly interaction energy of the ARG120-ligand calculated to be -17.1 kcal/mol. Thus, the substituents at 5,6 position of pyrazine ring suggests that these sybstituents would enhance the activity, this can be correlated with the presence of ARG120 that can from a salt bridge type of strong electrostatic interaction or the Pi electron-cation stacking with ARG120.

View full abstract

Phenothiazines and phenoxazines show biological activity including antipsychotic activity or carcinogenic activity. However, the target receptors for these compounds are still uncertain. To search for the target receptors, the comprehensive search algorithm (cASE) was introduced into MOE and 11,491 receptors were selected at random from Protein database using Molecular Database Calculator in MOE. Conformational search of fluphenazine was calculated and saved in a database, ultimately contains 74 conformers using MMFF94x force field in MOE. Molecular docking was carried out the most stable conformer and the unstable conformer of fluphenazine using the newly cASE module in MOE. As docking results of 11,491 receptors-two conformers of fluphenazine, the U_dockScores of 1,241,478 obtained by two conformers of fluphenazine into the active site of 10,358 target receptors. Among the docking structures obtained, DAO (PDB code 2E48) might be related to antipsychotic activity. ASEDock performed docking studies of DAO-416 conformers of phenothiazines and phenoxazines. In order to clearly the interaction of the receptors-ligands, the InterFragment Interaction Energy (IFIE) analysis was calculated by Fragment Molecular Orbital method. We discussed on the results of the IFIE analysis, and compared with the docking structure using GOLD.

View full abstract

As the solution to air pollution of the exhaust gas of Plants and cars, an exhaust amount of air contaminants is strictly controlled now. From the environmental criteria about air contaminants, it demands the gas sensors that can reach up to ppb(gm-3) of magnitude in detecting the gas is subject to control. In some recent works, it is shown that an electroconductivity of semiconductive carbon nanotubes (CNTs) is increased due to the adsorption of NO2 molecules on the CNT surface. It is expected that the mechanisim enables us to develop a new CNT-based sensor to defect NO2 molecules in the exhaust fume. In this study, we used first-principles calculation to investigate the mechanism of increasing in conductivity of NO2-adsorbed CNT. As the result, the local density of states (LDOS) distribution shows that the contribution of π orbitals to the electron conductivity is larger than that of α orbitals. Additionallly, in the LDOS of the NO2-adsorbed (7,0)CNT, the density of states around the energy of π orbitals of CNT is increased. It is consider that this leads to increasing of the conductivity of CNT.

View full abstract

The HOMO-LUMO gaps in armchair carbon nanotubes with Stone-Wales defect were calculated with PM3 method. It was found that the HOMO-LUMO gaps in armchair carbon nanotubes with Stone-Wales defects in two different orientations show an oscillatory behavior with a period of 3 with the increase of the number of carbon layers along the tube axis.

View full abstract

There are a number of chemicals which are harmful to human health as well as ecological systems. And some of them have been emitted to the environment. Although various systems and tools for evaluating environmental risk of chemicals have been developed, most of them require the information of the experimental values of chemical and physical properties as the parameters for the evaluations. Thus, it is difficult to evaluate the environmental risks of various chemicals of which only a few parameters have been obtained. The purpose of this study is to develop the system which enables us to evaluate environmental risk for a wide variety of chemicals. In this study, we try to introduce calculated values from a predictive model instead of experimental values into an evaluation system for environmental fate of chemicals. In addition, we tried to adopt the prediction errors of the calculated values to the evaluation systems, since the introduction of the prediction errors was expected to avoid wrong evaluations due to the prediction errors of the parameters. We used KOCWIN included EPI Suite developed by U. S. Environmental Protection Agency as a predictive model and MuSEM developed by National Institute for Environmental Studies as an evaluation system for environmental fate of chemicals.

View full abstract

In synthetic study it is ideal for chemists to examine an exhaustive synthetic route map before starting laboratory work. As commercially available information retrieval systems, SciFinder and Reaxys are commonly used. In our company we are also serving SYNSUP, which is an original synthetic route design system. First, the characteristics and benefits of those systems are briefly described. SYNSUP proposes possible routes for a given target molecule non-interactively. It is accessible via e-mail through both intranets and the Internet. SYNSUP could present new multi-step route candidates by use of reaction rules compiled based on reaction examples in literature. On the other hand reaction information retrieval systems are used to find literature for a particular query, where we have a certain reaction scheme, or a product and some requisite to the reactant in mind. SciFinder and Reaxys are found complementary due to their different coverage of references and kinds of data. To conclude, the combination use of SYNSUP, SciFinder and Reaxys is the most effective to obtain a comprehensive synthetic route map.

View full abstract

In order to examine the inversion of aromaticity between the singlet and the triplet states for the pi-conjugated intramolecular resonance-assisted hydrogen-bond system DFT calculations were carried out on 2-hydroxycyclohexadienones fused position-isomerically with m-membered (m=3,5,7) pi-conjugated rings. The HOMA indices on the basis of the bond alternation in the outer pi-conjugated rings for the acene-type compounds depended on m reversely to those in the singlet state, and were very sensitive to the positional isomerism. Those for the helicene-type compounds depended on m reversely to those for the acene-type ones, though their sensitivity to the positional isomerism was not apparent. The inversion of aromaticity in the triplet state compared to that in the singlet state was obviously elucidated with the NICS values on the basis of the NMR chemical shifts particularly for the 6-memebered rings. The positional isomerism for the NICS values was unfortunately indefinite. The HOMA indices and the NICS values for the present system indicated the enhancement of not only aromaticity but anti-aromaticity for the hydrogen-bond forms compared to the corresponding non-hydrogen-bond forms.

View full abstract

In the development of highly efficient organic light-emitting diodes, carrier-transporting materials with a high mobility and a low energy dissipation. It is necessary to reduce vibronic couplings in a molecule. A concept of vibronic coupling density enables us to control vibronic couplings. In this presentation, we will present a design principle of carrier-transporting molecules and novel electron-transporting molecules as examples.

View full abstract

Carbon dioxide capture and storage (CCS) is widely performed as one of measures against global warming. In the present CCS, however, cost of carbon dioxide capture is high, and therefore it is strongly required to develop more effective absorbing method. Chemical absorption method with amine compounds which have hydroxyl grope is one of the potent methods for carbon dioxide capture. For decreasing the cost of carbon dioxide capture, novel amine compounds with high capability of absorption and diffusion is required. Hence, the objective of this study is to explore such amine compounds. To construct regression models for predicting the absorption rate and the amount of diffusion of amine compounds, we evaluated the amine compounds whose properties are measured, applying semi-empirical molecular orbital method. By using this method, steric effect and electric nature can be considered. After constructing regression models by the GAPLS (genetic algorithm based-partial least squares) method in which choice of predictive variables is carried out, we evaluated amine compounds which are virtually generated with a structure generator. By using their properties estimated with the GAPLS models, we explored novel amine compounds with desirable properties.

View full abstract

The attrition of new drugs in development due to toxicity remains high. Therefore, it becomes more important that prediction of toxicity at an early stage for avoiding attrition during drug development. For rough toxicity prediction, it is efficient to use quantitative structure-activity relationship for ordered categorical data. However it is known that analyzing ordered categorical data in accurately is difficult with existing methods because they treat their objective parameters as nominal instead of ordered. We have already reported the development of the Boosting-ERDA (Evolved Regression Disciminant Analysis) method, which was developed by combining the ERDA method with AdaBoost. The ERDA method is used to generate models for ordered categorical data and AdaBoost is an ensemble learning. Our method has both accuracy and generalization capability at the same time. In this study, we have made an improvement in the Boosting-ERDA method to acquire information by calculating coefficients of explanatory variable. To evaluate performance of our new method, we have applied the Boosting-ERDA method for QSAR analysis of multi-drug resistance reversal agents using a data set of 609 compounds.

View full abstract

RNAi is a specific gene silencing mechanism triggered by siRNA. The application of RNAi for gene diseases requires the development of safe and effective delivery systems. For this reason, development of transfection reagents has been expanding. A transfection reagent is a lipid which introduces siRNA into a cell efficiently. We need to predict adequate structures for development of efficient reagents, because the efficiency of introducing siRNA into a cell and the rate of gene silencing differ depending on the structures of reagents. However, the structure-activity relationship has not been clear yet. We therefore proposed a chemoinformatics approach predicting the rate of gene silencing on transfection reagents from the structure by using a regression model constructed with database of transfection reagents. In this study, descriptors as explanatory variables in construction of the model were calculated with the softwares, DRAGON and CODESSA, and an objective variable was their Luciferase expression in the HeLa cell. By using a genetic algorithm based-partial least squares method, which is one of the variable selection methods, a high predictive model could be constructed with a small number of explanatory variables.

View full abstract

A new series of aromatic cyanovinyl compounds were synthesized via one-pot reactions of tri- or tetracyanoethylenes with nucleophilic reagents. The ground-state geometries and UV?vis absorption spectra of the compounds were computationally analyzed by means of density functional theory (DFT) and time-dependent density functional theory (TDDFT) calculations, respectively. None of the compounds were fluorescent in solution, but some showed intense emission in the solid state. The first excited singlet states (S1) potential energy surfaces (PESs) were explored using complete active space SCF (CASSCF) calculations for the compounds in order to elucidate nonradiative decay mechanism that takes into account the involvement of conical intersections (CI).

View full abstract

The computational estimation of DJ-1 protein and three ligands are presented. Fragment Molecular orbital (FMO) method was employed to compute the protein-ligand binding energies,supplemented with MM-PB(GB)SA method to estimate polarized and non-polarized salvation energies along with entropy based on molecular dynamics simulations. The explicit calculation of dispersion term was performed in FMO-MP2 level.

View full abstract

Accuracy-controlled 2nd-order convergence method has been presented for accurate quantum chemical calculations based on molecular orbital method, and has been found to provide us an efficient method for obtaining accurate molecular orbitals.

View full abstract

Large-scale density functional (DF) calculations were made possible by both high-performance computers and an efficient quantum chemical calculation algorithm. The exchange correlation (XC) term in the DF calculation is generally estimated by numerical integral scheme. Even though the accurate scheme is proposed for small molecules, the effectiveness is not verified enough for large-scale molecules like proteins. For the analysis of molecular properties such as chemical reaction, vibration spectrum, and so on, the integral scheme is demanded on 0.01~0.1 kcal/mol accuracy. The more accurate integral scheme is assumed to be required for the calculation of the huge molecules because those have a lot of electrons to accumulate the numerical error. In our previous study, we evaluated the accuracy of the various integral schemes by a single and a few amino-acid residues, and found that increasing the number of grids did not necessarily raise accuracy, and traditional three-dimensional numerical quadrature did not keep the rotational invariance. In this study, the relation of rotation and calculation accuracy of grids was clarified in detail for the improvement in accuracy of numerical integration.

View full abstract

Molecular docking is one of the most popular and most promising methods for virtual screening. However the heavy CPU cost prevents from applying it to the large compound library. Therefore, preliminary compound selection typically must be done before using molecular docking. We have planned to develop a new preliminary compound selection method and our unsuccessful feasible study suggested that DUD, typically used benchmark data set for virtual screening, might be unsuitable for our purpose. In this study, we have comprehensively calculated descriptors of DUD ligands and decoys using CDK, the open source cheminformatics tools, and analyzed their distributions. For some targets, the distributions of descriptors of decoys are smaller than those of ligands and sometimes included by ligands. It suggests that there are few decoys to reject by our selection method for the targets and using the whole DUD data set is not suitable for evaluating our compound selection procedures. We propose alternative benchmark data sets for the preliminary compound selection methods.

View full abstract

Extensive studies on fullerene derivatives have been made for the application in material science. Recently, we found that one of the series of N-methoxyethoxyethyl-2-(substituted phenyl)fulleropyrrolidine derivatives worked as a good acceptor partner in a P3HT-based thin film solar cell giveing the a high power conversion efficiency. However, the guiding principle for such high efficiency is still unclear. Density functional calculations have been performed for a series of fulleropyrolidine derivatives 1 with various substituents. A considerable positive correlation is found between the orbital energy of LUMO of 1 and the open circuit voltage (VOC) of the polythiophene-based solar cells in which the derivatives 1 are utilized as an acceptor material. This fact suggests that the VOC of the solar cells is subjected to the LUMO level of the derivatives 1. Moreover, the LUMO energy is lowered with increasing the Hammett constant of the substituent on the benzene ring in the derivatives 1. Therefore, we can predict the relative value of the VOC in the polythiophene-based solar cells.

View full abstract

Binding free energy ΔGbind of a ligand to the target protein is a physicochemical quantity which closely relates to a drug activity, and prediction of ΔGbind with accuracy leads to an efficient drug design. As a method to calculate ΔΔGbind, difference of ΔGbind between two ligands, FEP (free energy perturbation) and TI (thermodynamic integration) methods are well known. Theoretically, application of these methods are limited to the system where an energy difference is small, ~2 kcal/mol. Recently, Jorgensen et al. have applied these methods to a lead optimization study of HIV reverse transcriptase inhibitors, and succeeded in obtaining a qualitative relationship between the predicted and experimental values. However, it is desirable to establish an appropriate calculation procedure of these methods which reproduces experimental ΔΔGbind quantitatively. In this study, we applied the FEP/TI methods to the FXa (activated blood coagulation factor X) inhibitors, where one hydrogen atom on an inhibitor molecule was replaced with a chlorine atom. Several calculation procedures have been tested.

View full abstract

Recently, the studies on nanoscale molecules which operate similarly to the silicon devices such as transistors and switches attract much attention since such molecules enable the further miniaturization of devices. For example, a single-row phenyl chain is expected to be expressed switching function by rotating phenyl rings. In this study, we examined the switching function of 1,4-biphenyldithiol and 4,4'-terphenyldithiol using first-principles electron-transport property calculation. As the results, the electron-transport properties of phenyl chain exhibit two conduction channels, where one channel shows broad peaks and the other represents sharp ones in the transmission traces. Broad peaks are disappeared by rotating phenyl ring with twist angle of 90° where the delocalized π bondings between the phenyl rings are broken. On the other hand, the sharp peaks remain with high conductivity even though the twist angle becomes 90°. This gives rise to increasing of electric power consumption and destabilization of the molecules caused by the off-state leakage current. Therefore, it is necessary to control the contribution of such channels to electron conduction.

View full abstract

In the field of diagnostic imaging, discriminations between patients and normal subjects have been widely-studied using some statistical approaches for the purpose of clinical diagnostic support. However, there are not enough studies which proposed to discriminate a disease from others among patients. In this study, we tried to discriminate Alzheimer's disease from Parkinson's one by applying support vector machine (SVM) to the single photon emission computed tomography (SPECT) brain images. First, we compared blood flows between Alzheimer's and Parkinson's diseases by the one-sided t-test at each voxel and extracted the voxels whose p-values were <0.01, which constructed the dataset for this study. Then these voxels were divided into the subsets based on brain functions. Secondly, we applied SVM to the dataset with selecting the subsets by means of forward selection. The accuracy rates were 98% and 86% calculated by leave-one out cross validation and external validation methods, respectively. In addition, the brain regions where remained as significant using forward selection were consistent with the SPECT findings obtained previously.

View full abstract

The many-body interaction energies between nucleobases of DNA were calculated by means of ab initio MO method. We performed ab initio MO calculations for 2 and 3 base-pair steps in the conformations of A-DNA and B-DNA. To construct the stacking conformation for a base-pair in DNA, the geometry optimization was performed for each base-pair (A-T and G-C). Each many-body term in the interaction between nucleobases was obtained in the conformation of the stacked base-pairs. All the calculations were done with the theoretical level of MP2/6-31G(d). Additionally, the calculations in 2 base-pair steps were done with the theoretical level of RI-MP2/aug-cc-pVDZ. As for the interaction between bases, we found that the two-body term is dominant and each many-body term value depends on the base sequence. The calculated interaction energies, i.e. the hydrogen bonding between the bases and the stacking interaction between the base-pairs, were used to estimate the stability of DNA oligomers (ΔE) with various base sequences. Good correlation was found between the estimated ΔE values and the experimental ΔG values. This indicates that the internal energy of DNA oligomer can be estimated from summing-up of the constituent hydrogen bonding and the stacking interaction energies according to the base sequence.

View full abstract

An icosahedrally symmetric virus capsid is a molecular assembly of 60 identical protomers. Therefore, geometrical analysis on rotation axes, protomer position, etc., in icosahedral symmetry is always needed for preparation and analysis of simulation of icosahedrally symmetric capsids. This analysis is simple, but is not possible without detailed knowledge of geometrical properties of icosahedral symmetry. The author developed a new program, CAPAXIS, for the purpose to analyze geometrical properties, using the standard rotation matrices and rotation axes, the partition planes, the partition tables, the cell number function, etc., which have been clarified through the authors' development of rotational symmetry boundary condition. CAPAXIS has an UNIX-like command interface and can perform various calculations following the command line parameters. CAPAXIS is developed as free software following the GNU license. Classifications of the coordinate systems adopted for all the 85 files of icosahedrally symmetric capsid structure deposited to the Protein Databank are analyzed by CAPAXIS and the coordinate systems were classified into 3 groups.

View full abstract