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Design Optimization of Photoelectrode Reactor for Hydrogen Production by Combining CFD Simulation and Statistical Methods 基于CFD模拟与统计相结合的光电极制氢反应器设计优化
Pub Date : 2011-01-01 DOI: 10.2751/JCAC.12.1
Y. Maeda, K. Funatsu
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引用次数: 0
Advanced PLS Technique Focusing on Visualization and Chemical Interpretation - SOMPLS Analysis of Serine Protease Inhibitors - 聚焦于可视化和化学解释的先进PLS技术-丝氨酸蛋白酶抑制剂的SOMPLS分析
Pub Date : 2010-01-01 DOI: 10.2751/JCAC.11.56
K. Hasegawa, K. Funatsu
In quantitative structure activity relationships (QSAR), partial least squares (PLS) are of particular interest as a statistical method. Since successful applications of PLS to QSAR data set, PLS has evolved for coping with more demands associated with complex data structures. Especially, PLS variants focusing on visualization and chemical interpretation are highly desirable for molecular design. In this paper, we employed the self-organized map PLS (SOMPLS) approach to predict multiple inhibitory activities against three serine protease receptors (Factor Xa, Tryptase and urokinase-type Plasminogen Activator (uPA)). Retrosynthetic Combinatorial Analysis Procedure (RECAP) fingerprints were used as chemical descriptors that express the existence of specific substructure in the molecule. From the SOMPLS analysis and the subsequent correlation map, essential fragments for each serine protease were easily identified. From the correlation map, we designed best combinations of fragments at each substituent position for each serine protease protein. The essential fragments could be validated from X-ray crystal structures of serine protease receptors in computer graphics. SOMPLS is an unique approach that makes data-mining feasible from visualization of structure-activity data biased to ligand-based view point.
在定量结构活度关系(QSAR)中,偏最小二乘(PLS)是一种特别有趣的统计方法。由于PLS在QSAR数据集上的成功应用,PLS已经发展到能够处理与复杂数据结构相关的更多需求。特别是,专注于可视化和化学解释的PLS变体非常适合分子设计。在本文中,我们采用自组织图谱PLS (SOMPLS)方法预测了对三种丝氨酸蛋白酶受体(Xa因子、胰蛋白酶和尿激酶型纤溶酶原激活物(uPA))的多重抑制活性。利用反合成组合分析程序(RECAP)指纹图谱作为表达分子中特定亚结构存在的化学描述符。从SOMPLS分析和随后的相关图中,很容易确定每个丝氨酸蛋白酶的基本片段。从相关图中,我们为每个丝氨酸蛋白酶蛋白的每个取代位置设计了最佳的片段组合。丝氨酸蛋白酶受体的x射线晶体结构可以在计算机图形学中验证其基本片段。SOMPLS是一种独特的方法,使数据挖掘从结构-活性数据的可视化到基于配体的观点变得可行。
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引用次数: 1
Ab initio MO Study of Hydrogen Bonding and Spectral Characteristics of HCN-H2O-HCN Trimer: Comparison between Dimer and Trimer HCN-H2O-HCN三聚体氢键和光谱特性的从头计算研究:二聚体和三聚体的比较
Pub Date : 2010-01-01 DOI: 10.2751/jcac.11.36
Tomoya Takada, Shugo Ohshita
Hydrogen bonding of HCN-H2O-HCN trimer has been studied by means of ab initio molecular orbital (MO) calculations. The changes in intermolecular interaction energy and vibrational frequency induced by addition of HCN molecule to HCN-H2O or H2O-HCN dimer are especially focused. The distances of hydrogen bonds in the trimer are calculated to be shorter than those in the corresponding dimers. The hydrogen bond distances are hence shortened by addition of another HCN. The interaction energies of the hydrogen bonds are also increased by addition of HCN. The dipole moment of the trimer is smaller than the sum of the dipole moments of the separate moieties (HCN + H2O + HCN). This is opposite of the previous result for H2O-HCN-H2O. The spectral shift of the stretching modes induced by hydrogen bond formation has been predicted by vibrational frequency analysis. The vibrational frequency of the asymmetric stretching mode of HCN included in the H2O-HCN part of the trimer is remarkably red-shifted from that of the H2O-HCN dimer. This information is expected to be useful for experimental detection of the trimer.
用从头算分子轨道(MO)方法研究了HCN-H2O-HCN三聚体的氢键。特别关注了HCN分子加入到HCN- h2o或H2O-HCN二聚体中所引起的分子间相互作用能和振动频率的变化。计算出三聚体中的氢键距离比相应的二聚体中的氢键距离短。氢键的距离因此通过加入另一个HCN而缩短。氢键的相互作用能也随着HCN的加入而提高。三聚体的偶极矩小于HCN + H2O + HCN的偶极矩之和。这与之前H2O-HCN-H2O的结果相反。通过振动频率分析,预测了氢键形成引起的拉伸模式的谱移。三聚体中H2O-HCN部分HCN的不对称拉伸模式的振动频率与H2O-HCN二聚体的振动频率明显红移。这一信息有望用于三聚体的实验检测。
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引用次数: 0
Forest Learning Method for Chemical Education 化学教育的森林学习法
Pub Date : 2010-01-01 DOI: 10.2751/JCAC.11.1
M. Kaihara
化学は、理解する内容、記憶する内容、また計算力を必要とする内容などを含み、さらに、その原理原則も、電気分解や熱化学方程式、有機化学等、多種多様であることから、学生にとっては、比較的、取組みにくい科目と考えられている。筆者は、従来から、決定木、二進木等、樹木の構造を持つ回帰と分類の方法に関心を持ち、分類条件の探索や判別に応用している。この二進木は、集団学習法の一つ、RandomForestsやboostingの一種、MART(Multiple Additive Regression Trees)等に進化し、高い精度を持つ分類と回帰の方法へと発展した。特に、MARTの、学習率を低くするほど、短時間で高い精度が得られるという特徴、「遅いが早い」という逆説を、化学の教育に活用できないだろうかと考えた。具体的には、オープンエンド型の発想法、マインドマップと、問題解決を見据えた収束型の発想法、思考展開図を併用し、細かな問いかけ(ステップ)の積み重ねによって全体像を把握しようとすることによって、化学の理解深化や知識の定着と授業のコンパクト化を目指す試みである。マインドマップは、樹木の幹と枝葉のような構造を持ち、また、MARTは、簡素な幼木が一列に整列した林に例えられることから、森(マインドマップの集合)と林の概念を基盤とした学習教材とその方法として「森(森林)」と呼称した。H21 年度、SPP(サイエンスパートナーシッププログラム)にて、体験学習講座を開催した結果についても、併せて報告する。
化学包括需要理解的内容、需要记忆的内容以及需要计算能力的内容等,而且其原理原则也包括电解、热化学方程式、有机化学等多种多样的内容,对学生来说是比较难对付的科目。被考虑着。笔者一直对决策树、二进树等具有树木结构的回归和分类方法感兴趣,并将其应用于分类条件的探索和判别。这个二进树是集体学习法的一种,RandomForests和boosting的一种,MART(Multiple Additive Regression)Trees)等,并发展为具有高精确度的分类和回归方法。特别是MART具有学习率越低,就越能在短时间内获得高精确度的特点,即“慢而快”的反论,能否将其运用到化学教学中呢?具体来说,就是同时使用开放式结局型思维法、思维导图和以解决问题为目标的收敛型思维法、思考展开图,通过积累细微的提问(步骤)来把握整体情况,这就是化学原理。这是一种以解深化、知识巩固和课堂紧凑化为目标的尝试。思维导图的结构就像树木的主干和枝叶,而且MART被比喻成由一排简朴的幼树组成的树林,因此,以树林(思维导图的集合)和树林的概念为基础的学习教材和方法是“树林(森林)”林)”。H21年度,SPP(科学伙伴计划)举办体验学习讲座的结果也一并报告。
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引用次数: 1
A Theoretical Study on the Temperature Control of Fabrication of Pentacene Thin Film Transistors from Soluble Pentacene Precursors 可溶并五苯前驱体制备并五苯薄膜晶体管温度控制的理论研究
Pub Date : 2010-01-01 DOI: 10.2751/JCAC.11.62
Kazuaki Yoshimura, R. Ishikawa, H. Miyazaki, Atsushi Kawata, Michinori Sumimoto, K. Hori
ペンタセンを用いた塗布型有機半導体素子の作成法として、可溶性のペンタセン前駆体を塗布し逆Diels-Alder反応によりペンタセン骨格から脱離基を脱離させペンタセン薄膜へ転換する方法が提案されている。脱離基を変えた多くの前駆体に対して実験が行われ、それぞれペンタセンへの転換温度が異なることが示された。この転換温度と脱離基構造の関係を明らかにするため、報告されている6つの前駆体からペンタセンが生成する反応の解析を行った。その結果、活性化エネルギーEaが低い前駆体ほど転換温度が低い傾向にあることが明らかとなった。また重回帰解析を用いた検討により脱離基の最低非占有軌道(LUMO)と反応熱ΔEが低いほどEaが低いと計算された。次に、塗布成膜時に残存した溶媒の影響を調べるため、水素結合が形成される位置にメタノール分子を配置して、反応解析を行ったところ、Eaが気相中と比べわずかではあるが(最大で0.7 kcal mol-1)低下することが判明した。これは、前駆体の脱離基設計に加え展開溶媒として用いた分子の寄与を考慮することで、より転換温度の低い成膜プロセスが提案できる可能性を示している。
作为使用五射线的涂覆型有机半导体元件的制作方法,提出了涂覆可溶性的五射线前体,通过逆Diels-Alder反应从五射线骨架中脱去脱去基团转换为五射线薄膜的方法。对改变了离去基团的许多前体进行了实验,分别显示了向五烯转换的温度不同。为了明确转换温度和离去基结构的关系,研究人员分析了从6个报告前体生成五烯的反应。结果表明,活化能Ea越低的前体,其转换温度越低。另外使用了重回归分析研究解吸基础的最低非占有轨道(lumo)和反应热狄拉克δe越低ea低和计算的。接着,为了调查涂膜成膜时残余溶剂的影响,在形成氢键的位置配置甲醇分子,进行反应分析的结果,Ea与气相中相比虽然很少(最大0.7 kcalmol-1)降低。这表明,考虑到前体的离去基设计以及作为展开溶剂使用的分子的贡献,有可能提出转换温度更低的成膜过程。
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引用次数: 0
Bayesian Classification of Cytochrome P450 3A4 Substrates/Non-substrates and Color Mapping for Chemical Interpretation 细胞色素P450 3A4底物/非底物的贝叶斯分类和化学解释的颜色映射
Pub Date : 2010-01-01 DOI: 10.2751/jcac.11.19
Kiyoshi Hasegawaa, Kimito Funatsub
Prediction of cytochrome P450 (CYP) 3A4 substrates is valuable for finding promising drug candidates and a considerable amount of attention has been devoted to in silico predictions. Machine learning (ML) methods have recently been explored for perfoming ligand-based approaches. ML methods utilize supervised learning methods such as neural networks, support vector machines and Bayesian approaches to develop statistical models. In this paper, we used Bayesian approach to classify CYP 3A4 substrates and non-substrates. The extended connectivity fingerprint (ECFP) descriptor was used as chemical descriptor. The atom score was calculated from the Bayesian score of each fingerprint. By visualizing the atom scores with five graded-colors, the color mapping for each compound was performed. This can be used for chemical interpretaion why the specific compound exhibits CYP 3A4 substrate. The established Bayesian model and the associated color mapping would be useful for avoiding the risk of CYP 3A4 substrate in early drug discovery. The parallel use of the prediction of oxidation sites in the subsequent paper can give us de novo prediction of any molecules concerning CYP 3A4.
细胞色素P450 (CYP) 3A4底物的预测对于寻找有前途的候选药物是有价值的,并且大量的注意力已经投入到计算机预测中。机器学习(ML)方法最近被探索用于执行基于配体的方法。机器学习方法利用监督学习方法,如神经网络、支持向量机和贝叶斯方法来开发统计模型。本文采用贝叶斯方法对CYP 3A4底物和非底物进行分类。采用扩展连通性指纹(ECFP)描述符作为化学描述符。原子分数由每个指纹的贝叶斯分数计算得到。通过可视化原子分数与五个分级颜色,每个化合物的颜色映射被执行。这可以用于化学解释为什么特定化合物显示CYP 3A4底物。建立的贝叶斯模型和相关的颜色映射将有助于在早期药物发现中避免CYP 3A4底物的风险。在随后的文章中平行使用氧化位点的预测可以给我们关于cyp3a4的任何分子的从头预测。
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引用次数: 0
Development of a Pharmacophore Modeling Method and its Application to Phosphodiesterase-4 Inhibitors 磷酸二酯酶-4抑制剂药效团建模方法的建立及其应用
Pub Date : 2010-01-01 DOI: 10.2751/JCAC.11.44
Masamoto Arakawa, M. Shoda, K. Funatsu
新規医薬品の開発には多くの費用と時間を要するため、その効率化が強く望まれており、そのための有力な方法のひとつが、コンピュータと情報化学を利用して医薬品開発を行うインシリコ創薬である。特に、創薬プロセスの初期段階であるリード探索は、創薬プロセス全体の効率に大きな影響を与えるため、バーチャルスクリーニングによって質の高いリード化合物候補を発見する試みが数多く行われている。バーチャルスクリーニングを行うためのひとつの方法は、既知のリガンドからファーマコフォアモデルを構築し、それをもとにバーチャルライブラリの探索を行うことである。タンパクの立体構造を必要とせず、リガンドのみの情報で解析が可能であるという利点を持っている。ファーマコフォアモデルに基づくバーチャルスクリーニングにおいては、いかにして妥当なファーマコフォアを設定するかが重要であり、これまで様々な手法が提案されているが、決定的な手法は確立されていないのが現状である。そこで我々は、Hopfieldニューラルネットワークを利用して分子構造の重ね合わせを行うことによってファーマコフォアモデルを構築する手法を提案した。そして、その有用性を検証するため、Phosphodiesterase-4(PDE4)の阻害剤についてファーマコフォアモデルの構築を行った。活性を持つことがすでに知られている6つの阻害剤について配座探索を行い、得られた複数の配座のすべての組み合わせについて構造の重ね合わせを行った。そして、その重なりの度合いを指標として活性配座の推定を行い、ファーマコフォアを決定した。得られたファーマコフォアについて、PDE4のX線結晶構造を用いた検証を行った結果、活性部位の構造特徴を的確にとらえた妥当なモデルであることが確認された。
由于新药品的开发需要大量的费用和时间,因此人们迫切希望提高其效率,为此最有力的方法之一就是利用计算机和信息化学进行药品开发的insiliko创药。特别是作为药物开发过程的初期阶段的线索搜索,会对整个药物开发过程的效率产生重大影响,因此很多人尝试通过虚拟筛选来发现高质量的候选线索化合物。进行虚拟筛选的方法之一是,从已知的配体构建pharmacofour模型,以此为基础进行虚拟库的搜索。其优点是不需要蛋白质的立体结构,仅凭配体的信息就可以进行分析。在基于pharmaccofour模型的虚拟筛选中,如何设定合理的pharmaccofour是非常重要的,目前已经提出了各种各样的方法,但还没有确立起决定性的方法。就是这样。因此,我们提出了利用Hopfield神经网络,通过进行分子结构的叠加,构建pharmaccofour模型的方法。然后,为了验证其有效性,对Phosphodiesterase-4 (PDE4)的抑制剂构建了pharmaccofour模型。我们对已知具有活性的6种抑制剂进行了位点搜索,并对得到的多个位点的所有组合进行了结构重叠。然后,以重叠程度为指标,推测活性位点,确定了法马科夫。对得到的pharcofour,使用PDE4的X射线结晶结构进行验证的结果,确认是准确捕捉活性部位结构特征的合理模型。
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引用次数: 0
Excitation Energies of Stacked DNA Base Pair 堆叠DNA碱基对的激发能
Pub Date : 2010-01-01 DOI: 10.2751/JCAC.11.25
Muneaki Kamiya
The excitation energies of uracil dimers have been calculated with the configuration interaction singles (CIS) method, the configuration interaction with single excitations with perturbed doubles (CIS(D)) method, the equation-of-motion coupled-cluster method with singles and doubles excitations (EOM-CCSD), and the time-dependent density-functional theory (TDDFT) with pure and hybrid functionals. It is shown that the charge transfer excitations behave as 1/R at large molecular distance limit and the local excited states are split by the so-called electronic couplings. The calculated excited energies by the ab initio methods (CIS, CIS(D), EOM-CCSD) well reproduce those features. But the results of TDDFT cannot show those features because of the short-sightness of exchange correlation functionals of DFT. The inclusion of the electron correlation is crucial to the excitation energies, especially to the charge transfer excitation, of which the excitation energies are decreased by more than 2 eV.
用单组态相互作用(CIS)法、单组态相互作用(CIS(D))法、单双激发运动方程耦合簇法(eem - ccsd)和含纯泛函和杂化泛函的时变密度泛函理论(TDDFT)计算了尿嘧啶二聚体的激发能。结果表明,在大分子距离极限下,电荷转移激发为1/R,局部激发态被所谓的电子耦合分裂。用从头算法(CIS, CIS(D), EOM-CCSD)计算的激发态能较好地再现了这些特征。但由于交换相关函数的短视性,TDDFT的结果无法显示这些特征。电子相关的包含对激发能,特别是电荷转移激发至关重要,其激发能降低了2 eV以上。
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引用次数: 1
Ecotoxicity Prediction Using 3D Descriptors 利用3D描述符进行生态毒性预测
Pub Date : 2010-01-01 DOI: 10.2751/JCAC.11.11
日高 伸之介, 白石 寛明, 大眉 佳大, 山崎 広之, 岡本 晃典, 川下 理日人, 安永 照雄, 高木 達也
A vast quantity of chemicals are present in our environment and are considered indispensable to our high technological society. However, there are some chemicals that are hazardous and that can extensively impact both human health and the global environment. In Japan, ecotoxicity tests of chemical substances have been conducted with the goal of contributing to the Organization for Economic Cooperation and Development (OECD) evaluation program for harmful high-production volume (HPV) chemicals since 1995. To date, only about 500 compounds have been tested. There is a possibility that quantitative structure-activity relationships (QSARs) may enable us to predict environmental toxicities and fates as well as the physical and chemical properties of compounds; therefore, the toxicity prediction by QSARs is a possible alternative to the measurements of their ecotoxicities. In this study, we generated QSAR models from toxicity tests of Daphnids using only 3D descriptors to examine the availability of particular 3D descriptors for predicting of the ecotoxicity of compounds with various structures. Predicton accuracy of the model generated in this study was adequate and improved compared to that of the model using only the n-octanol/water partition coefficient, logP(o/w).
大量的化学物质存在于我们的环境中,被认为是我们高科技社会不可或缺的。然而,有些化学品是危险的,可能对人类健康和全球环境产生广泛影响。在日本,自1995年以来进行了化学物质的生态毒性试验,目的是为经济合作与发展组织(经合组织)有害高产量化学品评价方案作出贡献。到目前为止,只有大约500种化合物进行了测试。定量构效关系(qsar)有可能使我们能够预测环境毒性和命运以及化合物的物理和化学性质;因此,利用qsar进行毒性预测是替代其生态毒性测量的一种可能选择。在这项研究中,我们仅使用3D描述符从水蚤的毒性测试中生成QSAR模型,以检查预测具有不同结构的化合物的生态毒性的特定3D描述符的可用性。与仅使用正辛醇/水分配系数logP(o/w)的模型相比,本研究生成的模型的预测精度是足够的,并且有所提高。
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引用次数: 1
Selective Search Focusing on Retro-Synthetically Important Bonds in A Synthesis Design System 在一个合成设计系统中聚焦于逆向合成重要键的选择性搜索
Pub Date : 2009-01-01 DOI: 10.2751/JCAC.10.104
A. Tanaka, T. Kawai, T. Takabatake, Hideho Okamoto, M. Bersohn
A new capability has been added to the synthesis design system SYNSUP [1]. The new module generates synthetic routes that focus on key-bonds. Key-bonds are selected according to their spatial relationships to chiral atoms and central atoms of functional groups. When the key-bonds cannot be formed by any reaction known to SYNSUP, then structure changes in the vicinity of the bonds are effected so that the key-bonds can be disconnected in a retro-synthetic pathway. We called the fashion “selective search”. Such structure changes were studied, using 27 reported total synthesis of 25 naturally occurring compounds. This kind of selective search has been shown to be useful and practical for relatively complicated molecules.
一个新的功能被添加到合成设计系统SYNSUP[1]。新模块生成的合成路由关注于键。根据键与手性原子和官能团中心原子的空间关系选择键。当键不能通过SYNSUP已知的任何反应形成时,键附近的结构变化就会受到影响,因此键可以在逆转录合成途径中断开。我们称这种时尚为“选择性搜索”。这种结构的变化进行了研究,使用27报道的总合成25天然存在的化合物。这种选择性搜索已被证明对相对复杂的分子是有用和实用的。
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引用次数: 1
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