Chem-Bio Informatics Journal最新文献

{"title":"Optimal damping algorithm for unrestricted Hartree-Fock calculations","authors":"J. Yamamoto, Y. Mochizuki","doi":"10.1273/cbij.14.14","DOIUrl":"https://doi.org/10.1273/cbij.14.14","url":null,"abstract":"We have developed a couple of optimal damping algorithms (ODAs) for unrestricted Hartree-Fock (UHF) calculations of open-shell molecular systems. A series of equations were derived for both concurrent and alternate constructions of alpha- and beta-Fock matrices in the integral-direct self-consistent-field (SCF) procedure. Several test calculations were performed to check the convergence behaviors. It was shown that the concurrent algorithm provides better performance than does the alternate one.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2013-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77292539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cheminformatics workflows using mobile apps","authors":"A. Clark, Antony J. Williams, S. Ekins","doi":"10.1273/CBIJ.13.1","DOIUrl":"https://doi.org/10.1273/CBIJ.13.1","url":null,"abstract":"We are perhaps at a turning point for making cheminformatics accessible to scientists who are not computational chemists. The proliferation of mobile devices has seen the development of software or ‘apps’ that can be used for sophisticated chemistry workflows. These apps can offer capabilities to the practicing chemist that are approaching those of conventional desktop-based software, whereby each app focuses on a relatively small range of tasks. Mobile apps that can pull in and integrate public content from many sources relating to molecules and data are also being developed. Apps for drug discovery are already evolving rapidly and are able to communicate with each other to create composite workflows of increasing complexity, enabling informatics aspects of drug discovery (i.e. accessing data, modeling and visualization) to be done anywhere by potentially anyone. We will describe how these cheminformatics apps can be used productively and some of the future opportunities that we envision.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2013-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80580584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Over-Sampling Method and its Application to Cancer Classification from Gene Expression Data","authors":"Xuan Tho Dang, Osamu Hirose, Duong Hung Bui, Thammakorn Saethang, Vu Anh Tran, L. A. T. Nguyen, T. K. T. Le, Mamoru Kubo, Yoichi Yamada, K. Satou","doi":"10.1273/CBIJ.13.19","DOIUrl":"https://doi.org/10.1273/CBIJ.13.19","url":null,"abstract":"One of the most critical and frequent problems in biomedical data classification is imbalanced class distribution, where samples from the majority class significantly outnumber the minority class. SMOTE is a well-known general over-sampling method used to address this problem; however, in some cases it cannot improve or even reduces classification performance. To address these issues, we have developed a novel minority over-sampling method named safe-SMOTE. Experimental results from two gene expression datasets for cancer classification (i.e., colon-cancer and leukemia) and six imbalanced benchmark datasets from the UCI Machine Learning Repository showed that our method achieved better sensitivity and G-mean values than both the control method (i.e., no over-sampling) and SMOTE. For example, in the colon-cancer dataset, although the sensitivity and specificity achieved by SMOTE (81.36% and 88.63%) were lower than for the control method (81.59% and 89.50%), safe-SMOTE in contrast had these values increase (81.82% and 90.50%). Similarly, the G-mean value of the control (85.45%) decreased to 84.91% when SMOTE was employed, but increased to 86.04% when using safe-SMOTE. In the leukemia dataset, SMOTE was able to improve the sensitivity and G-mean values with respect to the control; however, safe-SMOTE achieved noticeable, even greater improvements for both of these criteria.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90106552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling of Human Neuraminidase-1 and Its Validation by LERE-Correlation Analysis","authors":"Seiji Hitaoka, Y. Shibata, Hiroshi Matoba, A. Kawano, M. Harada, Mustafizur Rahman, D. Tsuji, T. Hirokawa, K. Itoh, Tatsusada Yoshida, H. Chuman","doi":"10.1273/CBIJ.13.30","DOIUrl":"https://doi.org/10.1273/CBIJ.13.30","url":null,"abstract":"Four human neuraminidases (hNEUs1–4) have been identified. Among them, hNEU1 has been studied extensively as a target for sialidosis. It has been desired to understand the biological functions of hNEU1 at the molecular and atomic levels. The three-dimensional structure of hNEU1 is not known at present. In the present work, we constructed a three-dimensional structure of hNEU1 by homology modeling, and then performed correlation analyses between observed and calculated free-energy changes (quantitative structure−activity relationship (QSAR) analyses), coupled with LERE (linear expression by representative energy terms) procedure using the modeled three-dimensional structure in order to confirm the validity of the modeled structure. The atomic coordinates of all atoms in the verified model of hNEU1 are available. The proposed structure of hNEU1 will be useful and helpful for further studies concerning the biological and chemical functions of hNEU1. The present article is one of continuous works derived from the one that won the CBI","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89543709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design strategy for an initial state-independent diversity generator","authors":"Ryoji Sekine, D. Kiga, M. Yamamura","doi":"10.1273/CBIJ.12.39","DOIUrl":"https://doi.org/10.1273/CBIJ.12.39","url":null,"abstract":"Initial state-independent phenotypic diversification will be a powerful tool for directing cells to multiple phenotypes in practical situation, in which initial cellular states are unknown. In this study, we designed Symmetric Diversity Generator (SDG) for the initial state-independent phenotypic diversification, in which homogenous cells diversify into two phenotypes and the ratio of the phenotypes do not depend on the initial cellular state. The SDG consists of two mechanisms: an intracellular mutual inhibition by repressors and an intercellular activation of the repressor productions by intercellular activators that are expected to compensate imbalance of repressor concentrations and of intercellular activator concentrations. We computationally evaluated the initial state dependence of the SDG in terms of the ratio of the two phenotypes after the diversification, and found the SDG still has initial state dependence. For lower dependence, we designed two kinds of symmetric diversity generator focusing on degradation rate of activators and responsiveness of repressor productions to transcription factors, activators and repressors. Our computational evaluation suggests that the latter approach is much more promising than the former one because the intercellular activators can compensate the imbalance of the transcription factors in advance of response of repressor productions. The former approach would be used for improvement of robustness of other synthetic genetic circuits already designed.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2012-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90229403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal Lipophilicity of Sulfonium p-Toluenesulfonate as Anti-allergic Drug","authors":"Y. Tada, I. Yamawaki, S. Ueda, H. Matsumoto, N. Matsuura, M. Yasumoto, A. Koda, M. Hori","doi":"10.1273/CBIJ.12.25","DOIUrl":"https://doi.org/10.1273/CBIJ.12.25","url":null,"abstract":"In the development of the anti-allergic drug Suplatast Tosilate (IPD-1151T) we have reported the QSAR analysis using only the calculated values, because the few logK values of sulfonium compounds had been measured till then. In this study, we measured the logKTLC value of sulfonium compounds by using octylsililated silicagel plate (Merck HPTLC RP-8 F254S). The logKTLC values of the optimized compounds 52 and 67 (Suplatast Tosilate) of dimethylsulfonium p-toluenesulfonates derivatives were 0.07 and 0.06, respectively. Therefore, it was found that the desirable logKTLC value of the sulfonium compound was approximately zero as the anti-allergic drug.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89430785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rational design and engineering of protein A to obtain the controlled elution profile in monoclonal antibody purification","authors":"S. Yoshida, D. Murata, S. Taira, Keita Iguchi, M. Takano, Yoshiyuki Nakano, K. Minakuchi","doi":"10.1273/CBIJ.12.1","DOIUrl":"https://doi.org/10.1273/CBIJ.12.1","url":null,"abstract":"Biopharmaceutical monoclonal antibodies (Mabs) show different chromatographic behaviors in the elution step on protein A chromatography, although Mabs have similar three-dimensional structures. It is well known that interactions of conventional protein A to the V H 3 subfamily variable region negatively affect Mabs elution properties. The mutation G29A is known to weaken this binding, although not always sufficiently. We designed novel protein A mutations, S33E and D36R, by a computer-aided evaluation based on the three-dimensional structure. These mutations are expected to not only eliminate protein A binding to the variable region of Mabs but also to maintain its alkaline stability, which is required for effective CIP (Clean in place) of the protein A affinity matrix. In view of the superior potential of C domain, an in vitro study was performed with the G29A mutant of C domain (C-G29A) as a model protein. Both pentameric C domain mutants (C-G29A/S33E.5d and C-G29A/D36R.5d) showed little binding ability to the V H 3 subfamily variable region of Mabs by BIACORE analysis. We used a C-G29A/S33E.5d-immobilized matrix to confirm that the elution profile of Mabs belonging to the V H 3 subfamily at pH 3.5 was significantly improved. This matrix also showed almost the same alkaline stability as did the C-G29A.5d-immobilized matrix. The engineered protein A ligand, whose binding ability to the variable region is completely eliminated, would enable the separation of Fab fragments in flow-through fractions from Mab digestions. Rational design by a computer-aided evaluation should enhance the efficiency of protein ligand engineering. -9.0 T (Thr) +23.9 (-3.3) +0.9 +15.4 (-9.9) -5.0 The results of the mutations at residue Ser-33 or Asp-36 of C domain are shown. As for the complex, another result by adjusting the relatively high dielectric constant is shown in parentheses ( ). The negative  G of the mutants (Fab complex or free-state) indicate better thermostability than the case of the respective wild type. Hence, in this study, the positive  G complex is preferable in a complex to eliminate the binding to Fab, while the negative  G free is preferable in the free","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76924682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Docking of Barbital Enantiomers to the Nicotinic Acetylcholine Receptor:Implications for the Mechanism of Anesthesia","authors":"T. Seto, Masayuki Ozaki, S. Nosaka","doi":"10.1273/CBIJ.12.14","DOIUrl":"https://doi.org/10.1273/CBIJ.12.14","url":null,"abstract":"全身麻酔薬の開発には分子標的、作用機序の解明が必要である。GABAA受容体は意識消失の重要な分子標的候補のひとつである。しかし、いまだ明確な分子標的の特定や作用部位の特性は未解決のままである。そこで、麻酔薬が作用し、詳細な3次元構造が分かっているGABAA受容体類似のモデル標的に着目し、対掌体麻酔薬の結合部位における適合性を調べれば、麻酔作用部位における麻酔薬の分子認識の特性が推定できると考えた。ニコチン性アセチルコリン受容体をモデルに使用して、amobarbital, 対掌体バルビタルisobarbital, pentobarbitalの結合様式(position, orientation, conformation)をドッキングシミュレーションの手法を用いて解明した。その結果、いずれのバルビツルもアゴニスト結合部位に結合し、対掌体RとSの結合はバルビツル酸環が重なる位置関係に結合した。バルビツル系麻酔薬の結合はバルビツル酸環が主な結合力になっていることがわかった。すなわち、対掌体麻酔薬といえども、受容体との主要な結合力がその不斉点を含まない部分構造に由来する場合、不斉炭素が存在してもその分子識別への寄与は相対的に小さくなることが判明した。本研究の範囲では、薬物と受容体の相互作用のほとんどがバルビツル酸環部分に依るものであり、側鎖アルキル鎖の不斉中心に起因する立体的な構造の差異は薬物結合力に大きな差異を生み出さなかった。麻酔作用部位でも同様に側鎖アルキル基の不斉点は結合力に大きな違いを生じない可能性がある。すなわち、バルビツル系麻酔薬の作用部位は対掌体の識別が弱い特性をもつと示唆された。","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82694822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an Analytical Pipeline for Optimizing Substrate Feeding and Eliminating Metabolic Bottlenecks","authors":"Yuki Kuriya, Shigemitsu Tanaka, G. Kobayashi, T. Hanai, M. Okamoto","doi":"10.1273/CBIJ.11.1","DOIUrl":"https://doi.org/10.1273/CBIJ.11.1","url":null,"abstract":"Attempts were made to design and develop an analytical pipeline for identifying ways of increasing the production of a target metabolite that combine an optimized substrate-feeding schedule with a strategy for identifying and eliminating bottlenecks in metabolic pathways. As a case study, the proposed analytical pipeline was applied to acetone-butanol-ethanol fermentation by Clostridium bacteria, a process that has attracted considerable attention as a metabolic system capable of producing butanol, a possible biofuel.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87518882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"デオキシニバレノールがS. cerevisiae PTC1変異株に及ぼす遺伝子発現変化の解析","authors":"忠 鈴木, 岩橋 由美子","doi":"10.1273/CBIJ.11.41","DOIUrl":"https://doi.org/10.1273/CBIJ.11.41","url":null,"abstract":"Deoxynivalenol (DON) is a secondary metabolite that is generated by Fusarium species, which seriously affects both humans and livestock. Protein synthesis inhibition and ribotoxic stress, caused by induction of the mitogen activated protein kinase (MAPK) cascade, are thought to be responsible for the majority of DON toxicity. However, as DNA damage has also been reported, it is necessary to clarify all sources of toxicity. In this study, we conducted a DON exposure test using the PTC1 yeast mutant with disrupted MAPK-related genes, and observed gene expression changes using DNA microarray analysis. Our results indicated changes in the expression of genes associated with protein synthesis inhibition, as well as with DNA damage. At the same time, genes related to the synthesis of folic acid, a coenzyme in DNA synthesis, were inhibited. To complement the dysfunction of these genes, the growth media was supplemented with folic acid. As a result, the recovery of growth was confirmed, although it was a consistent effect and it did not reflect differences in susceptibility to DON toxicity.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80470658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}