Chem-Bio Informatics Journal最新文献

{"title":"Functional genomics analysis of n-alkyl sulfates toxicity in the yeast Saccharomyces cerevisiae","authors":"S. Sirisattha, E. Kitagawa, M. Yonekura, H. Iwahashi","doi":"10.1273/CBIJ.8.69","DOIUrl":"https://doi.org/10.1273/CBIJ.8.69","url":null,"abstract":"The n-alkyl sulfates (AS) are a class of anionic surfactants that are widely used in industry and in consumer products. In this study, the effects of AS on yeast growth and genome wide transcriptional profiles were analysed by DNA microarray technology. Induced genes were categorized by localization of gene products and by function according to accepted gene ontologies using the MIPS database. A number of genes whose products localized to the cell wall and peroxisome were significantly induced. Genes involved in energy metabolism (i.e., fatty acid β-oxidation pathway) were also significantly induced. To confirm the role of these functions, the sensitivity of selected single gene deletion strains to sodium dodecyl sulfate (SDS) was tested. Deletion strains of cell wall maintenance genes (ΔGAS1, ΔKRE6, and ΔCHS5) were found to be highly sensitive. Interestingly, mutants deleted for genes in the fatty acid β-oxidation pathway were not found to be sensitive. However, regulating genes in the fatty acid β-oxidation pathway were found to respond to SDS exposure in a dose-dependent manner and to be involved in H2O2 production. Here, we report a functional genomics analysis of genome-wide expression data to screen and evaluate AS toxicity in yeast. While the approach begins with a determination of highly-induced genes, its power lies in then determining the most relevant functions targeted by AS, and then assessing loss of key genes by evaluating AS sensitivity in the corresponding deletion mutants.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"77 1","pages":"69-84"},"PeriodicalIF":0.3,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80373713","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":"Density, Diffusion, and Site-Dipole Field of Solvent around Four Types of Flavonoid Studid by Molecular Dynamics","authors":"丸山 慶一朗, 成敏 神谷, 永淑 尹, 彰 功刀, 剛 横溝, 順一 肥後","doi":"10.1273/CBIJ.8.33","DOIUrl":"https://doi.org/10.1273/CBIJ.8.33","url":null,"abstract":"We studied hydration of four types of small nonpeptidic molecule, flavonoid, by molecular dynamics simulations at 300 K with focusing on three physical quantities: solvent density, solvent site-dipole field, and solvent diffusion. The solvent site-dipole field is a quantity recently introduced by us to study directional ordering of water molecules around solute. The spatial patterns of these quantities showed strong site-dependency around the flavonoids. Common to the four flavonoids, high solvent-density sites around hydrophilic solute atoms were characterized by strong directional ordering of water molecule and by depressed solvent diffusive motions. Contrarily, high solvent-density sites around hydrophobic solute surface were characterized by weak directional ordering. The solvent site-dipole field showed specific ordering patterns of water molecules not only in the first solvent layer but also in the second solvent layer. The spatial patterns of the three quantities were conservative among the four flavonoids whether the intra-flavonoid flexibility was large or not. Thus, an adiabatic approximation, which has been assumed in various theoretical hydration studies, was satisfied well. The hydration at a site in the vicinity of solute was determined mainly by the physico-chemical property of the solute atom group nearest to the solvent site, which supports a phenomenological theorem that the solvent accessible surface area of a solute is proportional to the solvation free energy.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"30 1","pages":"33-48"},"PeriodicalIF":0.3,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74996294","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":"Integrated pharmacokinetic assessment and strategy for orally effective prodrugs overcoming luminal degradation and biological membrane barriers","authors":"T. Mizuma","doi":"10.1273/CBIJ.8.58","DOIUrl":"https://doi.org/10.1273/CBIJ.8.58","url":null,"abstract":"Because no kinetic principles have been proposed for designing orally effective prodrugs, the author recently reported a kinetic model for membrane transport of prodrugs (Chem-Bio Informatics Journal, 8, 25-32 (2008)), and proposed the kinetic classification and criteria for effective membrane-permeable prodrugs (KCCEMP). The present study addressed more practical conditions, where a prodrug is metabolized/degraded to a drug in the luminal tract after oral administration. Primary factors in orally effective prodrugs are luminal degradation/metabolism and absorption clearance (permeability), which includes the mechanism of membrane transport and metabolism in intestinal cells. The fraction of absorbed prodrug is expressed by the functions of these parameters. Based on the required improvement ratio of the absorption clearance, the kinetic classification and criteria of orally effective prodrugs (KCCOEP) are proposed as a decision tree with conditional equations for guiding kinetic assessment and strategy for the rational development of prodrugs. The assessment of lenampicillin, which was selected as an example of successful prodrugs, according to the procedure indicated a significant impact of luminal degradation/metabolism on the absorbed fraction, and suggests that most ester-type prodrugs on the market degrade in the luminal tract. Thus, a comprehensive study on the fraction of luminal degradation/metabolism and the absorption clearance (permeability) should be conducted to develop orally effective prodrugs, in particular, quantitative assessment of the fraction of contribution (fc,dd) of the drug formed from the prodrug in the luminal tract to the absorption following oral administration of the prodrug is emphasized.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"160 1","pages":"58-68"},"PeriodicalIF":0.3,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87866516","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":"Compound-Transporter Interaction Studies using Canonical Correlation Analysis","authors":"M. Kitajima, Yohsuke Minowa, H. Matsuda, Y. Okuno","doi":"10.1273/CBIJ.7.24","DOIUrl":"https://doi.org/10.1273/CBIJ.7.24","url":null,"abstract":"The efficient screening of lead compounds or drug candidates for efficacy and safety is critically important during the early stage of drug development. Compounds are usually screened from a diverse ‘chemical space’ based only on its pharmacological effects, but this screening is not enough to guarantee drug safety. To solve this problem, we devised a chemical space that takes into account interaction information with proteins such as drug transporters. We also created and evaluated a mathematical model for predicting compound-transporter interactions. This was achieved by first generating an interaction correlation matrix based on drug transporters and their corresponding inhibitor compounds. To implement a screening scheme that takes into account interaction with drug transporters, we created a model using Canonical Correlation Analysis (CCA) that makes use of the known information on interaction between drug transporters and their corresponding inhibitors. Cross-validation of the model gave satisfactory test results and a physiologically relevant chemical space was constructed based on the model.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"26 1","pages":"24-34"},"PeriodicalIF":0.3,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86640035","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":"Nuclear localization of proteins with a charge periodicity of 28 residues","authors":"N. Sakiyama, R. Ke, R. Sawada, M. Sonoyama, S. Mitaku","doi":"10.1273/CBIJ.7.35","DOIUrl":"https://doi.org/10.1273/CBIJ.7.35","url":null,"abstract":"Proteins with a charge periodicity of 28 residues (PCP28) were found recently in the human proteome, and many of the annotated PCP28 were located in the nucleus (Ke et al., Jpn. J. Appl. Phys. 2007). The physical properties of the amino acid sequences were analyzed to detect the difference in the physicochemistry between the nuclear and cytoplasmic PCP28 and develop a software system to classify the two types of PCP28. A significant difference in the global parameters from the entire sequence and the local parameters around a segment with the highest positive charge density was found between the nuclear and cytoplasmic PCP28. The global classification score included the densities of proline and cysteine, and the negative charge density, while the local score included the symmetry of the charge distribution, the density of cysteine, and the positive charge density. A prediction system was developed using the global and local scores, which possessed a sensitivity and specificity of 92% and 88%, respectively. The mechanism of translocation of proteins to the nucleus is discussed using the parameters relevant to the predictive system.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"8 1","pages":"35-48"},"PeriodicalIF":0.3,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81452987","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":"Implementation of the blue moon ensemble method","authors":"Y. Komeiji","doi":"10.1273/CBIJ.7.12","DOIUrl":"https://doi.org/10.1273/CBIJ.7.12","url":null,"abstract":"The blue moon ensemble method (Carter et al., 1989, Chem. Phys. Lett. 156, 472; Sprik & Ciccotti, 1998, J. Chem. Phys. 109, 7737) calculates the free energy profile of a chemical reaction along a specified reaction coordinate. The explicit algorithms for two simple reaction coordinates (“distance between two particles” and “difference between two distances”) are derived. The derived algorithms are presented by Fortran-like codes to facilitate their implementation in arbitrary programs.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"36 1","pages":"12-23"},"PeriodicalIF":0.3,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75226566","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":"Nuclear proteins with charge periodicity of 28 residues are specifically increased in vertebrate genomes","authors":"N. Sakiyama, R. Ke, R. Sawada, M. Sonoyama, S. Mitaku","doi":"10.1273/CBIJ.7.69","DOIUrl":"https://doi.org/10.1273/CBIJ.7.69","url":null,"abstract":"More than 36,000 open reading frames (ORFs) from the human genome were previously analyzed by the autocorrelation function of electric charge distribution, revealing the existence of many proteins with a charge periodicity of 28 residues (PCP28) (Ke et al., Jpn. J. Appl. Phys. 2007). The major component of PCP28 was located in the nucleus, and the nuclear PCP28 of ten vertebrate and seven invertebrate organisms were predicted with a novel software system (Sakiyama et al., CBI Journal 2007) for revealing the biological significance of nuclear PCP28. Retrieval of the features of the human nuclear PCP28 in Swiss-Prot revealed that almost 90% of nuclear PCP28 functions in transcriptional regulation, including hypothetical transcription factors. To study how nuclear PCP28 is increased in eukaryote genomes, we compared the number of all nuclear PCP28 in vertebrate and invertebrate genomes. The results showed that nuclear PCP28 is specifically increased in vertebrate genomes and that the ratio of other types of PCP28 is almost constant in all eukaryote genomes. These findings strongly suggest that nuclear PCP28 is an essential protein for vertebrate organisms.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"29 1","pages":"69-78"},"PeriodicalIF":0.3,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74685206","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":"Investigation of the relationship between sample size and risk factors for complex diseases based on a simulation study","authors":"Yasuyuki Tomita, M. Nakatochi, H. Asano, H. Izawa, M. Yokota, H. Honda","doi":"10.1273/CBIJ.7.1","DOIUrl":"https://doi.org/10.1273/CBIJ.7.1","url":null,"abstract":"The correlation between major disease factors and sample size remains an important question in clinical investigations. A small sample size results in the selection of falsely significant risk factors that are not derived from population data. This problem is more serious in studies on multifactorial diseases based on polymorphisms and environmental factors because these studies require combination analysis. In the present study, we defined threshold lines to identify risk factors comprising complex interactions based on sample size. These threshold lines were constructed by a simulation study based on a resampling method that comprised a large data set (1441 case subjects with myocardial infarction and 979 control subjects). Finally, we demonstrated that these threshold lines could be used to identify risk factors for different data sets. In conclusion, these threshold lines enable us to design an association study of multifactorial diseases based on combination analysis.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"30 1","pages":"1-11"},"PeriodicalIF":0.3,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83423328","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":"ケミカルバイオロジー/ ケミカルジェネティクス/ ケミカルゲノミクスにおけるケミカルライブラリーの重要性","authors":"文彦 九川, 勝 渡辺, 冬彦 玉野井","doi":"10.1273/CBIJ.7.49","DOIUrl":"https://doi.org/10.1273/CBIJ.7.49","url":null,"abstract":"A new field of science, chemical biology/ chemical genetics/ chemical genomics (cb/cg/cg) has emerged since the late 1990's, especially in the United States. The NIH Roadmap agenda, Molecular Libraries Screening Center Network (MLSCN), became a drive force to push cb/cg/cg forward. Cb/cg/cg studies consist of three methodologies, chemical libraries with small molecules, high-throughput screenings, and computational databases. In this review, we focus on the importance of chemical libraries. Natural products-originated chemical libraries or their synthesized related compounds-derived chemical libraries have long contributed to human health sciences in mainly pharmaceutical industries. The reason why natural products have been of interest is that they consist of diverse and complex chemical compounds. This character makes natural compounds important as the seed of future medicine. Currently, pharmaceutical industry-based chemical biology using biology-oriented chemical libraries has spun off into the cb/cg/cg studies for basic biology in non-profit scientific organizations and a variety of developments have resulted from the use of chemical libraries with natural products. To overcome the diversity and complexity of nature-originated chemical compounds, a new concept of synthesizing small chemical compounds, Diversity-Oriented Synthesis (DOS), has been established by Harvard chemist, Stuart Schreiber in late 1990's. Using split-pool synthesizing methodology, small molecules produced by DOS make it possible for us to obtain compounds that span a wide chemical space. Here, we discuss cb/cg/cg studies applied to signal transduction, stem cell differentiation and small G-protein researches. All of these studies are conducted not only using biology-oriented libraries but also DOS-oriented libraries. Although cb/cg/cg is a relatively young science that aims the post-genome era sciences, it must bridge chemistry and biology not only in the academia but also in pharmaceutical industries. genetics, chemical library, chemical genomics, Chemical Biology Platform at Broad Institute, chemical space, commercially-available chemical library, diversity and complexity, Diversity-Oriented Synthesis (DOS), focused library, geranylgeranyltransferase-I inhibitors, high-throughput screen (HTS), independent screening facilities, library of libraries, Molecular Libraries Screening Center Network (MLSCN), natural products, NIH Roadmap, Peter Schultz, RIKEN NPDeo, small G-protein, small molecules, Stuart L. Schreiber, σ-element, Target-Oriented Synthesis (TOS), UCLA chemical compound library, UCLA MSSR","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"9 1","pages":"49-68"},"PeriodicalIF":0.3,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88681088","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":"The evaluation of environmental waters using yeast DNA microarray","authors":"Y. Murata, Satomi Murata-Mizukami, E. Kitagawa, H. Iwahashi, K. Takamizawa","doi":"10.1273/CBIJ.6.29","DOIUrl":"https://doi.org/10.1273/CBIJ.6.29","url":null,"abstract":"We propose a new method for the evaluation of environmental water by using DNA microarray technology. Twenty-one types of environmental waters were sampled from incineration processes, some factories, and various soils. We performed a comprehensive analysis by DNA microarray, and attempted to classify the environmental water samples by hierarchical cluster analysis. These water samples were classified into clusters from A to F together with chemicals and physical stress conditions. The water sample that grouped into cluster A caused protein denaturation and oxidative stress, but not mutagenesis. The water samples that grouped into cluster B caused protein denaturation. The water samples that grouped into cluster C caused mutagenesis, protein denaturation, and cell wall damage. The water samples that grouped into cluster D caused mutagenesis. The water samples that grouped into cluster E caused protein denaturation and oxidative stress. The water samples that grouped into cluster F caused oxidative stress. Consequently, the potential influences of environmental water could be estimated by hierarchical cluster analysis.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"38 1","pages":"29-46"},"PeriodicalIF":0.3,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89532952","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}