Chem-Bio Informatics Journal (Chem Bio Informat J)
Description
- WebsiteChem-Bio Informatics Journal website
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ISSN1347-6297
Publications in this journal
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Article: Validation of Techniques for Structure Prediction and Thermostabilization of a Protein: A Case Study Using the TIM-barrel Enzyme Lactate Oxidase
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ABSTRACT: Recently, a variety of methods for protein structure prediction have been developed. However, there are only a limited number of studies where the results have been adequately validated. With this in mind, we have evaluated our previously predicted model of lactate oxidase by comparison with the recently determined crystal structure. In addition, we also analyzed our thermotolerant mutants that were designed on the basis of a predicted model. The validity of these procedures was assessed by comparing the results of rational design against the interpretation of the thermostabilization mechanism. Specifically, we analyzed lactate oxidase (LOX), a useful lactic acid sensor, as an example for validation. LOX was chosen because it has an (/) 8 barrel (TIM barrel) fold, which constitutes the basic structural framework of numerous important enzymes. We also propose an effective modeling method and thermostabilization technique for the TIM barrel fold.Chem-Bio Informatics Journal 01/2009; 99:62-7462. -
Article: Validation of ArgusLab Efficiencies for Binding Free Energy Calculations
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ABSTRACT: We conducted a docking efficiency validation of ArgusLab, a free docking software program. In this study, the calculated binding free energies of protein-ligand complexes by scoring functions were compared with experimental binding affinities. Correlations between the calculated and experimental data were evaluated for 11 ArgusLab settings and compared. Our results indicate that ArgusLab is useful for virtual screening and the weight of van der Waals interactions are unimportant for binding free energy calculations using this software.Chem-Bio Informatics Journal 01/2009; 9(9):52-6152. -
Article: Structural studies of coenzyme Q10 inclusion complex with γ-cyclodextrin using chemical analyses and molecular modeling
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ABSTRACT: The stability, dispersibility and oral bioavailability of coenzyme Q10 (CoQ10) are known to be improved upon complexing CoQ10 with -cyclodextrin (-CD). However, the details of the three-dimensional structure of the -CD/CoQ10 complex are not well understood. Therefore, the molecular composition and three-dimensional structure of the complex were investigated using chemical analyses and molecular modeling. The molecular ratio of -CD and CoQ10 in the complex was investigated by NMR as well as by HPLC to determine the -CD/CoQ10 ratio of 2.5. DSC analysis of the -CD/CoQ10 complex indicated formation of the inclusion complex. Three different complex models (-CDx2+CoQ10; -CDx3+CoQ10; -CDx5+CoQ10x2) that correspond to the derived -CD/CoQ10 ratio were also constructed and then molecular mechanics and dynamics calculations were carried out to provide several possible complex structures. Based on the complex structures thus obtained, structural and energetic features of the complexes were examined.Chem-Bio Informatics Journal 01/2009; 99:1-111. -
Article: Gene expression profile of MAP kinase PTC1 mutant exposed to Aflatoxin B1: dysfunctions of gene expression in glucose utilization and sphingolipid …
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ABSTRACT: Aflatoxin B 1 (AFB 1) is a harmful and cancer-causing mycotoxin generated by Aspergillus flavus. Its mechanism of toxicity has not been fully clarified and further research is required. In this study, we attempted to further clarify aflatoxin B 1 toxicity using the results of S. cerevisiae gene expression analysis. In a Ser/Thr phosphatase 2C disruptant (ptc1Δ) with weakened activity of anti-toxic components (cell wall and membrane), the addition of low concentrations of sodium dodecyl sulfate resulted in elevated susceptibility to AFB 1 . From the microarray results, expression changes in DNA synthesis or repair, sphingolipid metabolism, glucose metabolism, and cell wall-related genes were well detected. Our results indicate that AFB 1 causes sphingolipid metabolism disorder, leading to dysfunction in signal secretion and inhibition of efficient glucose metabolism, which supplies the materials for cell wall proteins and cellular components, resulting in repression of the stress response to external toxicants.Chem-Bio Informatics Journal 01/2009; 9(9):94-10794. -
Article: A high performance prediction system of coiled coil domains containing heptad breaks: SOSUIcoil
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ABSTRACT: The coiled coil structure in proteins is characterized by heptad repeats of hydrophobic amino acids, but many breaks of the heptad repeats are observed within coiled coil regions which are the main cause of the errors in the currently used prediction systems for coiled coils. For understanding the characteristics of coiled coils including heptad breaks, the features of coiled coils were studies focusing on three problems: (1) the determination of appropriate register for the breaks in heptad repeat regions, (2) the discriminations of coiled coil regions using physical properties of amino acid segments which have heptad repeats and (3) the elucidation of the structural difference among several types of heptad breaks. Appropriate registers of heptad repeats and breaks were determined by two steps: first, the typical template of heptad repeats was applied to amino acid sequences and then several types of template for heptad breaks were applied to the segments around inconsistent points of the heptad repeat regions, leading to the most appropriate registers. Then, the coiled coil regions were discriminated from other types of regions by the canonical discriminant analysis, using ten parameters (three physicochemical properties and seven number densities of amino acids). The novel coiled coil prediction system SOSUIcoil showed better performances of coiled coil prediction than other prediction systems. Furthermore, the structures of segments around the heptad breaks were analyzed, indicating that some types of heptad breaks tend to form coiled coil structure whereas the other types are at the end of coiled coils.Chem-Bio Informatics Journal 01/2008; 8(8):96-11196. -
Article: Functional genomics analysis of n-alkyl sulfates toxicity in the yeast Saccharomyces cerevisiae
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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 H 2 O 2 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.Chem-Bio Informatics Journal 01/2008; 8:69-84. -
Article: Application of Rough Set Theory to High Throughput Screening Data for Rational Selection of Lead Compounds
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ABSTRACT: In the field of drug discovery, high-throughput screening (HTS) is widely used to identify new lead compounds. A considerable number of hit compounds, however, will subsequently be found to have low activities when their inhibitory activities are measured more precisely. Such compounds are called false positives. For a more efficient selection of lead compounds, virtual screening methods with QSAR models have been investigated, but no definitive solutions have been found. In this study, we propose an effective method to identify lead compounds. The proposed method is based on rough set theory (RST), which is a mathematical tool for depicting the uncertainty and vagueness of knowledge. The essential parts of RST are the construction of reducts, which are minimal subsets of variables to distinguish samples, and the extraction of rules using their reducts. By applying RST to the QSAR study of monoamine oxidase (MAO) inhibitors, we extracted several rules for identifying lead compounds. First, 3D-structures of MAO inhibitors were generated uniformly by CORINA, and chemical descriptors were calculated by the Volsurf method. Finally, three unique rules were extracted by using RST. It is found that the each rule is chemically reasonable and compatible with previous studies. Furthermore, the predictive power of RST was also proved by comparison with partial least squares (PLS) and decision tree (DT). These results demonstrate the usefulness of our method.Chem-Bio Informatics Journal 01/2008; 8(8):85-95. -
Article: Density, Diffusion, and Site-Dipole Field of Solvent around Four Types of Flavonoid Studid by Molecular Dynamics
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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.Chem-Bio Informatics Journal 01/2008; 8(8):33-4833. -
Article: Investigation of the relationship between sample size and risk factors for complex diseases based on a simulation study
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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.Chem-Bio Informatics Journal 01/2007; 7(7):1-111. -
Article: Nuclear proteins with charge periodicity of 28 residues are specifically increased in vertebrate genomes
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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.Chem-Bio Informatics Journal 01/2007; 7(7):69-7869. -
Article: Chemical biology/Chemical genetics/Chemical genomics: Importance of chemical library
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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.Chem-Bio Informatics Journal 01/2007; 7(7):49-6849. -
Article: Compound-Transporter Interaction Studies using Canonical Correlation Analysis
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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.Chem-Bio Informatics Journal 01/2007; 7(7):24-3424. -
Article: The evaluation of environmental waters using yeast DNA microarray
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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.Chem-Bio Informatics Journal 01/2006; 6(6):29-4629. -
Article: Statistical applications for SNPs analysis
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ABSTRACT: A subset of single nucleotide polymorphisms (SNPs) can be used to capture the majority of the information of genotype-phenotype association studies. The primary issue that we should discuss in SNPs analysis is how one can select a particular subset of SNPs while maximizing the power of detecting a significant association. From this point of view, we reviewed some statistical tools for SNPs analysis by focusing in this paper on the Hardy-Weinberg equilibrium, case-control association study, and haplotype estimation and association. We also paid special attention to the issue of how we can determine the required sample size by using the sequential test. With regard to the statistical tools for SNPs analysis, we reviewed the basic concepts of each method and its applications.Chem-Bio Informatics Journal 01/2006; 6:55-68. -
Article: BirdsAnts: A protein-small molecule interaction viewer
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ABSTRACT: A data-matrix viewer, BirdsAnts, is developed for the effective visualization of large scale protein-small molecule interaction data. One of two design concepts is the simultaneous visualization of three kinds of data: data pertaining to proteins, those to small-molecules, and those to interactions between them. The other is switching of global and local views of data back and forth. To evaluate BirdsAnts, a data-matrix was generated by processing a protein-small molecule interaction database. Analyzing the matrix, two known facts were rediscovered. First rediscovery was the knowledge that each function of vitamin B12 is exercised by interaction to a different protein. Second was that cyclooxygenase inhibitors were correctly classified into known classes by two-step clustering calculations. The results of the evaluation show that BirdsAnts has future potential for the effective visualization of protein-small molecule interaction data.Chem-Bio Informatics Journal 01/2006; 6(6):17-2817. -
Article: FCANAL: structure based protein function prediction method. Application to enzymes and binding proteins
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ABSTRACT: Structural genomics projects are beginning to produce protein structures with unknown functions, thereby creating a need for high-throughput methods to predict functions. Although sequence-based function prediction methods have been used extensively, structure-based prediction is believed to provide higher specificity and sensitivity because functions are closely related to the three-dimensional structures of functional sites, which are more strongly conserved during evolution than sequence. We have developed FCANAL, a method to predict functions using a score matrix obtained from the distances between C α atoms and frequencies of appearance [1]. The previous report used key residues predicted from sequence comparisons (motifs). In this report, we have expanded the method to include enzymes and binding proteins with key residues predicted on the basis of three-dimensional structures. Using FCANAL, we constructed score matrices for 31 enzymes. When we applied them to all of the structure entries deposited in the Protein Data Bank, FCANAL could detect functional sites with high accuracy. This suggests that FCANAL will help identify the functions of newly determined structures and pinpoint their functionally important regions.Chem-Bio Informatics Journal 01/2005; 5(5):39-5539.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.
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