The dynamics of the drying process of a polymer solution droplet placed on a substrate is important in various modern technology, especially the ink-jet printing process. The process involves various challenging problems such as the transport of solvent and solute induced by solvent evaporation, the gelation and the contact line dynamics etc. We have been studying the phenomena the both experimentally and theoretically. In this talk, I will give an overview of our research.

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A mesoscale simulation of concentrated colloidal nanoparticles in a simple shear between parallel flat plates is carried out to investigate structure formation of the nanoparticles and rheology of the colloid. The motion of nanoparticles is calculated by an off-lattice Newtonian dynamics, and the flow of solvent is calculated by an on-lattice fluctuating Navier-Stokes equation. A fictitious domain method is used to couple the motion of nanoparticles with the flow of solvent. The present simulation counts all crucial interactions, such as contact force and torque, van der Waals force, electrostatic force, hydrodynamic force and torque including thermal fluctuation of the solvent that causes translational and rotational Brownian motions of the nanoparticles. Three-dimensional simulations at Peclet number of 100 and 1000 are performed. The results show that the aggregation of nanoparticles takes place as a function of Peclet number. The aggregated structure of nanoparticles changes considerably the velocity profile between the flat plates to a sigmoid curve, so that the apparent viscosity of colloid increases. The increment of apparent viscosity depends on the size of aggregated structure of nanoparticles.

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We have been developing the QM/MC method, Monte Carlo simulation using quantum mechanical (QM) calculations in order to investigate solvent effects for chemical reactions. The simulation uses the QM calculations to obtain energies of ensembles. Although MC simulations using fully quantum mechanical calculations are free from classical parameters, it takes long CPU times to obtain energies with statistical meanings. We developed a program which calculates difference of free energy of salvation connected with free energy perturbation (FEP) calculations. Activation free energies in solutions can be calculated using the QM/MC/FEP method. We adopted he droplet model that includes a solute molecule in its center and have solvent molecules around the solute within a radius depending on the sides of solvent molecules. The solute has structures optimized using quantum mechanical calculations. The QM/MC(B3LYP/6-311++G**//MP2/6-31G*,PM3,PM3) calculation gave activation free energies included solvent effects to be 12.7, 13.8 and 15.2 kcal mol-1 in aqueous, methanol and propane solutions, respectively. These results indicate that the rate of the reaction in aqueous solution is much faster than that in propane and is consistent with the experimental data.

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Recently development of fluorescent molecular probes attracts much interest for in-vivo medicinal analysis. One of the typical examples is the fluoroscein derivates called Tokyo Green (TG). In this work, excited states and electronic spectra of protonated and deprotonated forms of TG were theoretically investigated by using the time-dependent density functional theory (TDDFT). Here we focus on revealing structure-property relationship on chemical modification of the benzene moiety. It is shown that the TDDFT method successfully reproduces the experimentally observed excitation energies. The calculation reveals that there are two important excited states assigned as ?-?* and charge-transfer (CT) excited states. Depending on the functional group introduced in the benzene moiety, the excitation energy to the CT excited state changes. As a result, the CT excited state becomes lower than the ?-?* excited state in some molecules from which fluorescence is not observed. Since the CT excitation is electric-dipole forbidden, we predict that the energy lowering is the origin of quenching of fluorescence. The solvent effect of the excitation energies was also studied, indicating that it can also be a factor controlling the emission property of this series of compounds.

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A flexible organic molecule often crystallizes in more than one structure with characteristic packing arrangement respectively, and these crystal structures (polymorphs) show distinct physical, optical, or thermodynamic properties such as melting point, dissolution rate, morphology, and color. Therefore, analysis of polymorphism phenomenon for target molecule is quite important issue to obtain crystal with expected properties in development field of new functional materials or drugs. Recently, we have been developed CONFLEX/KESSHOU (CONFLEX/K) which can be performed analysis and prediction for conformational polymorphism of a flexible organic molecule. In this work, conformational polymorphism analysis of acetylsalicylic acid (aspirin) known as analgesic and anti-inflammatory drug was carried out using CONFLEX/K. As a consequence, aspirin conformers with s-trans carboxylic acid group generated hydrogen bonds like chain between neighboring molecules, and this chain motif was stable than dimer motif which were generated between s-cis carboxylic acid groups in experimental crystal structure.

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Because chemistry has characteristics, for example, quite complexity and diverse, we have difficulty when learning it, especially at first. When the more, we would like to learn chemistry, the more, we would face with the difficulty for understand the total concept of chemistry. In other words, we know, "you can't see the forest for the trees." Therefore, we propose Forest Learning Method (FLM) in order to understand the total image of chemistry. This is the application of the Thinking Figures Method and the Mind Map, dedicated to mainly idea processor. Both methods have similarities, for example, radial thinking methods, jointing a word and the other word, using arrows or branches. Much more, both methods recommend using a word or short sentences as possible as we can. This is because both were primary proposed for idea processors. In case of FLM, we would accept sentences or chemical equation because we would be able to learn chemistry, more continuously. We should say that FLM is specialized type of the Thinking Figures Method or the Mind Map for learning. As a result of applying FLM to students, we found that they would be able to learn each section of chemistry, for example, electrical chemistry, chemical equilibration and so on, more hierarchically, and totally.

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Molecular simulations using conventional force fields have been successful for understanding the nanoscopic behavior of molecules in several chemical environments. However, the classical approaches have some shortcomings due to the electrostatic interaction calculated by fixed atomic charges. To describe the charge reorganization due to nuclear structrural changes of the molecules, we developed the new charge equilibration (NQEq) framework and introduced it into molecular force field MMFF94s. For reproducing the relative energies of conformational isomers of the organic compounds obtained by MP4(SDQ) level, we refined the parameter set of torsion interaction term. The new force field, named MMFF/NQEq, can reproduce the conformational energies better than those by MMFF94s.

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We have investigated two methods for definition of applicability domain (AD) of quantitative structure - property relationships (QSPR) models. One of them is a range-based method which defines an AD by the ranges of several molecular descriptors. The other one is based on one-class support vector machines (OCSVM) which typically used for data domain description and outlier detection. We have built several QSPR models to evaluate robustness and stability of AD methods. We used two sets of organic compounds with experimental values of aqueous solubility; aliphatic mono alchol and herbicides. For both datasets, three regression models have been built: two partial least squares (PLS) models and an epsilon supprot vector regression (e-SVR) model. One of the PLS models was optimized via variable selection using genetic algorithm. The parameters of e-SVR model were selected via grid searching. Thus we have tested AD methods for various types of QSPR models; linier and non-linier, overfitted and optimized, local and global. As a result, we conclude using OCSVM can be suitable for definition of AD robust for various types of QSPR models.

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It is indispensable to investigate ADMET(absorption, distribution, metabolism, elimination, and toxicity) properties in the drug discovery process. Generally, examinations of metabolism take a long time in ADMET test process. Therefore, the method for predicting a metabolite of a drug candidate is strongly needed. In this study, we developed the method for predicting metabolites using chemoinformatics methods. In order to predict metabolites, we have to reveal mainly two selectivities: isoform specifity, which is the selectivity whether a molecule is metabolized by enzymes, and regioselectivity, which is the selectivity of the position where metabolic reaction preferentially occurred in a molecule by enzymes. We built both isoform specificity models and regioselectivity models by using several machine learning methods such as support vector machine and random forest. By applying isoform specificity models for a drug candidate, we can predict enzymes which metabolite it. By applying regioselectivity models for it, we can predict site of metabolism of the compound. Through this process, we can predict metabolites of drug cadidates.

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Quantitative Structure-Activity Relationship (QSAR) has been widely used in molecular design and many successful applications have been known. However, when precise model would be made, its chemical interpretation becomes difficult. Therefore, we have developed inverse QSAR system to generate chemical structures with high inhibitory activities. EA-Inventor (Evolutionary Algorithm-Inventor) was used as structure generator in our system. In EA-Inventor, initial structures represented by SMILES strings are modified using cross-over and mutation operations. The inhibitory activities are predicted by QSAR model and their values are used as the scores. The structures with high scores survive and next new structures are generated. After these cycles, the higher scored structures can be obtained. We have applied EA-Inventor to Trypsin inhibitory data. CoMFA (comparative molecular field analysis) is employed as QSAR model. If new structures differ from training set, high penalty values are added to scores in order to guarantee them within chemical space. The generated structures are high complementarily to Trypsin structure and the result seems to be reasonable. This technology can be extended to ADME model and chemical feasibility filter.

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We have developed a knowledge-based protein-ligand docking method. This method predicts 3D structures of a protein-ligand complex from each isolated structure by using database of experimentally solved 3D protein-ligand complex structures. We predicted for 114 protein-ligand pairs as a validation of our method. Here, we assumed that a prediction was accurate when root mean square deviation value between a predicted ligand structure and an experimentally solved structure was less than 2.0 angstrome. As a result of validation study, the number of accurately predicted complex was 59. In the case of prediction without homologue structures as background data, the number was 18. This method requires information about 3D structure of homologue protein for accurate prediction. On the other hand, when at least one accurately predicted structure was contained in the ranking top 100 conformations, the numbers of successful prediction were 88 and 104 by use of non-homologue and additional homologue structures as background respectively. This method is not sufficiently accurate but requires low computational costs because it avoids conformational search and potential energy calculation. This method is effective for a preliminarily filter for other docking program.

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Global warming from increasing atmospheric carbon dioxide is one of the most serious issues facing us today. We need to develop new technologies for resolving this problem. Although carbon dioxide capture and storage (CCS) is a promising solution for this problem, total cost should be reduced for practical realization In particular, cost of separation and recovery dominate a large part of total cost, development of more effective absorbing liquid is desired. The object of this study is to propose novel structures of alkanol amine for chemical absorption process of carbon dioxide. We used group contribution method to form explanatory variables, and constructed regression models for absorption rate and heat of reaction using PLS and SVR method. As a result, predictive SVR models were obtained for both objective variables. The R squared values and Q squared values are 0.828 and 0.646 for absorption rate, 0.813 and 0.578 for heat of reaction, respectively. Then, we carried out exhaustive search to find novel alkanol amines by changing the number of fragment systematically. As a result, we could obtain various candidates which may have more useful properties for absorption of carbon dioxide.

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Soft sensors are widely used to estimate a process variable which is difficult to measure online. One of the crucial difficulties of soft sensors is that predictive accuracy drops due to changes of state of chemical plants, catalyst performance loss, sensor and process drifting, and so on. In order to cope with this problem, a regression model can be updated with a new sample. However, if the model is updated with an abnormal sample, the predictive ability can deteriorate. We have applied the independent component analysis (ICA) method and support vector machine (SVM) to the soft sensor in order to increase fault detection and diagnosis ability. Then, we have tried to increase the predictive accuracy. By using the ICA and SVM based fault detection and diagnosis model, the objective variable can be predicted, updating the regression model appropriately. We analyzed real industrial data as the application of the proposed method. RMSE of a traditional soft sensor model are 0.511, and that of the proposed soft sensor model are 0.200. The proposed method achieved higher predictive and fault detection accuracy than the traditional one.

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Achiral and chiral alkanes (as three-dimensional structures) are classified into centroidal and bicentroidal alkanes. Then they are enumerated combinatorially, where inequivalence with respect to carbon contents and branching degrees (numbers of quaternary, tertiary, secondary, and primary carbons) are taken into consideration.

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Our conformational space search method, CONFLEX can efficiently produce large numbers of lower energy conformers of a given chemical structure. To find a particular quantity of interest, for example, structural relationships between the lower energy minima, flexibility of ligand conformations, special distributions of functional groups, and etc., one or some of clustering techniques are often used. However, when one would like to better understand how these conformers found by CONFLEX are related to chemically-important property of the molecule, the current visualization techniques to represent the complicated conformational space might be able to give us only too poor understandings. We introduce here our recent attempts on development of new visualization technique for more understandable conformational networks which are three-dimensionally expanded on a sphere.

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Cellular automaton simulations are interesting to investigate space-time patterns of systems consisting of various inter-component interactions. One of the typical simulations is the one based on the "Game of Life" algorithm (GLA) which was proposed by Conway. In the present paper, GLA is mathematically formulated and is generalized as a simulation tool for studying dependence of patterns by revising the algorithm for time evolution, changing the initial distribution ratio of the "ON" state (corresponding to "a life" at a cell), extending the range of the interaction, and taking into account the effect of fluctuation as a model for a realistic open system. In the present study, we monitor the number of the "ON" state, a number of steps to reach an equilibrium, and chemical potential in the simulated pattern by considering the interaction energy. In most cases, the number of the "ON" state cells decreases as the simulation step proceeds. Interestingly, we observed that, in some conditions, the number of the "ON" state increases. A variety of simulated patterns will be discussed and analyzed to understand a general trend in pattern formation in cellular automaton simulations.

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It is very important to occupy computational resources on parallel computers and clusters. For this purpose, we have developed a new grid computing system, the Gauss Grid, to schedule computational jobs and manage servers having various platforms and different configurations. It is specialized to operate jobs for quantum chemical calculations i.e., Gaussian03 jobs. The Gauss Grid system is constructed centering on a computer called the DataMaster. It takes hold of status of servers, receives inputted job offers by users, runs jobs on applicable servers and stores all data of any jobs. We adopted the PostgreSQL RDBMS for managing information of servers and jobs in the DataMaster. There were 6,526 calculation jobs between 10/1/2007 and 3/31/2008 in Hori laboratory, Yamaguchi University. 26 servers which have each 6 Pentium 4 2.6GHz class CPUs finished these jobs with 94.19% of working rate under the Gauss Grid. It was confirmed that the Gauss Grid was very useful for operating servers with high efficiency and easy to use by beginners with a simple GUI.

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Currently, the nuclear medicine image diagnostic methods such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) are used for the diagnosis of the brain disease into which regional cerebral blood flow changes such as Alzheimer's disease, Parkinson's disease and so on. In the brain disease, the early diagnosis is extremely important for good prognosis, and one of the effective means is SPECT inspection. Along with the development of the technology, statistical image analysis methods such as Statistical Parametric Mapping (SPM) and easy Z-score Imaging System (eZIS) have been developed. These techniques enable us to find the abnormal blood flow sites in the images. However, these techniques don't provide the estimations of the diseases. Then, we tried to develop the new technique for estimations of a disease. We examined whether a more objective diagnosis is possible in brain disorders by applying the multivariate analysis to cerebral blood flow SPECT data.

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In order to evaluate pi-conjugation effects on intramolecular resonance-assisted hydrogen bonds, DFT calculations were carried out on 1-carbonyl and w-hydroxyl substituted polyacenes fused with 3-, 5-, or 7-membered pi-conjugated rings. The pi-conjugation-length dependence of the stabilization energies due to the intramolecular hydrogen bonds and the barrier heights for proton transfer along the hydrogen bonds for the acenes with the fused 3- and 7-membered rings differs significantly from those for the acenes with the fused 5-membered ring. The O-H bond lengths in the intramolecular hydrogen-bonding conformation show similar, notable pi-conjugation-length dependence, whereas those in the non-hydrogen-bonding conformation are almost constant against the pi-conjugation length. The electron densities at the bond critical points of the O-H bonds indicate also similar behavior. The parameters for aromaticity, HOMA for the outer rings and NICS(1) at the 3-, 5-, and 7-membered rings both in the hydrogen bonding and non-hydrogen bonding conformations vary similarly and noticeably against the pi-conjugation lengths. These results were discussed on the basis of the intramolecular resonance-assisted hydrogen bonds with (4N+2) and 4N pi-conjugated electrons.

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Molecular dynamics simulation of the complex of the capsid of echovirus 1 and a pocket factor, i.e. palmitic acid (PLM), was performed under rotational symmetry boundary conditions, using the APRICOT program. Echovirus belongs to the picornavirus family, and are frequently responsible for febrile illness and viral meningitis. A milistic acid (MYR) is bound to the N terminal of VP4 of the capsid. The atomic charges of PLM and MYR were determined by the restrained electrostatic potential fit (RESP fit), using the electrostatic potential calculated at the HF/6-31G* level using Gaussian03. The protonation states of the 22 histidine residues in the X-ray structure (pdb-ID:1EV1) were determined by considering the neighbor atoms and by calculation with the protonate3D program of the modeling software MOE. Atomic fluctuations calculated from the simulation were compared with the temperature factor of the X-ray analysis of the capsid of a homologous echovirus 11, because temperature factors are not reported in 1EV1.

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Coxsackievirus A9, a human pathogen causing symptoms ranging from common colds to fatal infections of the central nervous system, is an icosahedral single-strand RNA virus that belongs to the genus Enterovirus of the family Picornaviridae. Molecular dynamics simulation was performed for the complex of the coxsackievirus A9 capsid and two molecules of antiviral drug, WIN51171, under rotational symmetry boundary conditions, using the APRICOT program. For the simulation, the protonation states of histidine residues in the X-ray structure (pdb-id:1D4M) were determined by considering the local structure around the residues and by calculation with the Protonate3D program of the modeling software MOE. Because the integrin binding site, i.e. the C-term of VP1 of the capsid, is disordered in the X-ray analysis, the initial structure of the site was taken from the X-ray structure of foot-and-mouth disease capsid. Electrostatic potential around WIN51171 and myristic acid that is bound to the N-term of VP4 was calculated with HF/6-31G* level. The two-conformational two-stage RESP fit was used to determine their atomic charges. The integrin binding site showed large fluctuation in the water zone over the outer surface of the capcid.

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The computational representations of chemical structures and the structure searching techniques are the basic methodologies of cheminformatics and have eagerly been studied since 1950?s. Based on these techniques, many organizations maintain the databases of their own compounds. In case of university, however, there seldom hold the organization-wide compound databases. This would be because the laboratories are basically independently managed and there are little needs for a organization-wide compound management. Currently, school-wide research collaboration project for lead finding and optimization is undertaken in our school and then the school-wide compound database is required. The requirements of the database will be differ from ones in pharmaceutical firms. We have developed a prototype database to determine the requisites of the compound databases used in the university. The prototype is developed using ChemAxon?s JChem 5.0.3 (2008), MySQL 5.0, and Apache Tomcat 5.0. The current status of the prototype database and the future plans will be presented.

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Under the circumstance of rapid progress of genome analyses, automatic identification of genes and operons, which are a set genes, are becoming still more important. The signal included in the operon may play an important role for identification of genes. Those signals are the terminator which is in the 3'-terminal of operon and Shine-Dalgarno sequence which is in the 5'-terminal of the operon. In the present report we developed the simple method for specifying terminators. The dot-matrix method, which has been used for the analysis of secondary structure of RNA, applied for the terminator sequence search with the free energy parameters as scores. Free energy parameters of Serra about successive base pairs were used. They were modified to adapt for experimentally identified terminators. Sixty nucleotides at the down stream of stop codon of all annotated E.coli K12 genes were extracted and used as candidates for terminators. Sequences with high score values included rich T regions, and low score sequences did not. It is conjectured that the former is the rho-independent terminator and the latter is the rho-dependent terminator.

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A convenient input tool for the chemical structural formula and the chemical reaction information management system were developed for the carbohydrate design support support system. A partial structural retrieval became possible by the character string composed of the mnemonic symbol of the monosaccharide and the uniting style between monosaccharides. The retrieval result of considering the 3-D structure around a reactive part can be obtained by using this system.

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When we investigate the stability and the structure of a molecule, it is important to take account of the flexibility of the molecule. Only the equilibrium structure, however, is often taken into account, which is a local minimum structure of one bottom of the potential energy surface. To get thermodynamics parameters, the vibrational partition function is often calculated based on the harmonic approximation with only the one local minimum structure. Especially, for a linear molecule, there are a lot of conformers in the range of small energy differences and with low transition energies. It is necessary to take those other conformers into consideration to assess the stability and structure of the molecule.Here we show how to take account of the flexibility of a molecule, and the computational results are given for the thermodynamics parameters of some linear molecules.

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Organic luminescent materials in solid state have been widely studied from the view point of their abundant applications to opt-electronics. We recently found that 2,2':6',2"-terpyridine (tpy) undergoes fluorescence on/off switching via heat-mode reversible conversion between the two different crystal structure (typ-N and tpy-P). While the switching is derived from the reversible transformation between two chemical structures, its detailed mechanism in molecular level is still unresolved. In this computational study, we calculated the ratio of non-radiative decay rate based on Fermi Golden Rule, where electronic coupling and Franck-Condon (FC) term were independently examined in detail. The slight difference in the molecular structure of tpy-N and tpy-P indicates the differences in the electronic coupling term is too small to play a definitive role in their drastic fluorescent behavior. We thefore focused on the FC-term and found the delicate balance between inner- and outer- reorganization energies and the driving force (the difference of Gibbs free energy between initial- and final states), which decisively affect the non-radiative decay rate.

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We have found that the reactivity trends observed for gas-phase OH radical reactions of nine halogenated cyclobutanes are strongly correlated with their C-H bond strengths. Our results have shown that a collision-theory-based kinetic equation with adjusted parameters reproduce well the rate constants of these OH radical reactions from the C-H bond dissociation enthalpies of the halogenated cyclobutanes. This kinetic equation was applied to estimate the rate constants for OH radical reactions of acyclic halogenated compounds in our previous study. Although the ring strain is likely to be related with the reactivity trends for the halogenated cyclobutanes, the best-fitted parameter values for the reactions halogenated cyclobutanes are found to be almost identical with those fitted for the reactions of acyclic counterparts. This result suggests that the effects of the ring strain should be reflected in C-H bond enthalpy values, and thus, without considering the effects of ring strain separately, we can estimate the rate constants for the OH radical reactions of acyclic halogenated compounds and those of halogenated cyclobutanes by using almost identical kinetic equation.

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It is well known that molecular properties, including biological functions, are closely related not only to the atomic connectivity but also to the 3D spatial arrangements of the atoms. In the present work, the hetero-atom filter reduced representation of a molecular structure was employed. Structural information of a molecule including its 3D geometry was represented by a weighted graph of which the nodes and edges correspond to hetero-atoms and the inter-atomic distances between them, respectively. To describe local 3D structural information of a molecule, the authors have defined the Hetero-tree representation, i.e., the minimum spanning tree (MST) of such molecular graph based on inter-atomic distances between hetero-atoms.We have prepared a target data set that contains 107 ester molecular structures taken from CSD. Each molecule of the data set contains from six to ten hetero-atoms, and was represented by its Hetero-tree. Structural feature searching was carried out based on the topological information of Hetero-trees. For example, there were 23 molecules that have the common Hetero tree, as n-hexane type. As a result, we successfully found the molecules that have the common structural feature based on Hetero-tree but quite different scaffold structures.

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The study of intermolecular interactions is a useful step toward gaining a basic understanding of the dynamic behaviour of molecules in various environments. In the present study, high-level ab initio calculations [MP2] using correlation consistent basis sets of Dunning [aug-cc-pVDZ, aug-cc-pVTZ] were carried out to study the potential energy surfaces of CH3OCH3/H2O, CH3OCF3/H2O and CF3OCF3/H2O Van der Waals dimers and to clarify the stable structures of these clusters. For the calculation of interaction energies, the basis set superposition errors (BSSE) were estimated by counterpoise method. One stable structure for CH3OCH3/H2O dimer has been found. For the optimized structure, the H2O molecule is outside the C-O-C plane of the CH3OCH3, and the bond angle O(CH3OCH3)---H-O(H2O) is approximately 180°. For the structure of CH3OCF3/H2O, we have found two stable structures in which the H2O molecule exists in the C-O-C plane of the CH3OCH3/H2O molecule. For the stable structure of CF3OCF3/H2O, the H2O molecule are located in the direction of the lone pair of the CF3OCF3 moleclule. The details of the potential energy surfaces are discussed.

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Artificial neural networks (ANN) have widely been used in chemical analysis of mixtures. In this work, ANN was applied to determining concentrations of halide anions or oxoanions (chloride, bromide, iodide, acetate, carbonate and sulfate) which are very similar in property to each other, and so it is quite difficult to do that. In this case, absorption spectra appear in a shorter wavelength region. Therefore, we used a sensor molecule (a cobalt(III) complex) which shows charge-transfer bands owing to ion-pair formation with the anions. The charge transfer absorption upon addition of an anion is somewhat different from other ones. Multilayer neural networks were chosen for pattern-recognition analysis. The architecture consists of input, output, and hidden layers, which are where data are processed through a back propagation training algorithm. Of the 25 spectra obtained, 24 of these were used to train the data set (charge-transfer absorbance) by using 21 wavelengths from each spectrum. When the remaining one unknown was processed, an absolute error of a few % was obtained for the output concentrations for the mixtures containing chloride and bromide, bromide and iodide, bromide and acetate, and then carbonate and sulfate.

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In our continuing efforts to compute biopolymers such as AIDS proteins, which are a major target for antiretroviral therapy, an all-electron quantum chemical calculation on the complexes of HIV-1 protease (HIV-1 PR) with its inhibitors has been carried out using ab initio fragment molecular orbital (FMO) method. Here, we extend this computational work with FMO method to further explore the relationship between computed binding energies and clinically reported drug effects for HIV-1 PR inhibitors, on the basis of the interaction of some human aspartyl proteases (human PRs) including renin and pepsin with HIV-1 PR inhibitors. Two inhibitor-bound renin PR complexes with Ritonavir and Saquinavir were each subjected to a FMO calculation at MP2/STO-3G level by using BioStation package. Ritonavir in the complex with the renin, which exists in human kidney, gave the largest binding energy and showed a relatively strong interaction with the renin catalytic active site residue ASP221. The present computations indicate that peptidomimetic PR inhibitors having a relatively large binding and interaction energy for human PRs as well as for HIV-1 PR can be highly effective as an AIDS agent but they can also produce unwanted side effects: renal and hepatic dysfunction and hyperglycemia (high blood sugar).

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Among chemicals existing in environments, very few are identified as carcinogens. But from the viewpoint of the animal protection, it becomes a social, urgent problem to develop a technology to predict the carcinogenicity of the chemicals from the structures. Up to now, a lot of researches have been done, but it is extremely difficult to predict the carcinogenicity of non-congeners with various chemical structures. In our previous study, relationships between carcinogenic ranks for many non-congeners and descriptors generated from their three dimensional molecular structures were analyzed using a support vector machine (SVM) technique, and it was concluded that SVM showed a satisfactory predictability for screening test using animals within short time, but its predictability power was inferior to an artificial neural network (ANN). In this study, SVM was combined with a decision tree method and an ensemble learning method to improve its predictability power, and it was shown that the combination led to a rather improvement in predicting the carcinogenicity of non-congeners from their structures.

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The capillary gas chromatograph column retention time under isothermal conditions was observed for 46 pentachlorobiphenyls. Relative changes of the partition enthalpy (Δ(ΔH)) and the entropy (Δ(ΔS)) were calculated from the plots of natural logarithm of the ration of capacity factor and the inverse of temperature, so called as van't Hoff plots. Although a linear relationship between Δ(ΔH) and Δ(ΔS) was observed, we judged the compensation effect was "classical type". Because the intersection points of the van't Hoff plots did not become a single point. To elucidate the dependence of Δ(ΔH) on the molecular surface area (SA), two classification parameters, the number of chlorine atoms substituted at 2, 2', 6, and 6' positions (Nor-Cl) and the number of a pair of proximitive chlorine atoms (Npx-Cl), were used. Δ(ΔH) was markedly classified on the basis on Nor-Cl, but little dependence on the SA was found. On the other hand, the classification on the basis of Npx-Cl revealed a marked linear dependence of Δ(ΔH) on SA.

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It is essentially important to understand fundamental concept of electronic effects from substituents to ionic centers for both controlling reactions and designing molecules. Aromatic carbocations are first stabilized or destabilized by inductive effects of every substituents, followed by stabilization by resonance effect of para-pi-electron-releasing substituents. These behaviors of ring substituents are well described by the Yukawa-Tsuno equation. In this paper, substituent effects of carboanionic systems are investigated in gas phase in order to make clear the intrinsic effects of the substituents. According to the Yukawa-Tsuno equation, significant resonance stabilization is expected in para-pi-electron attracting substituents. We used proton transfer reaction to determine the relative stabilities of benzylic anions. Electronic energies of species in these reactions were calculated by means of DFT method. The gas phase stabilities of benzylic anions with various alpha-substituents are available from the ICR experiment, and the experimental delta-G values can be reproduced precisely by the calculated delta-E values. We compared substituent effects on delta-E of these benzylic anions with one another, to discuss electronic effects of ring substituents in carboanionic systems.

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