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Wada M.,AOMi Inc | Wada M.,Fujitsu Limited | Kanamori E.,AOMi Inc | Kanamori E.,Hitachi Solutions | And 2 more authors.
Journal of Chemical Information and Modeling

We developed a new protocol for in silico drug screening for G-protein-coupled receptors (GPCRs) using a set of "universal active probes" (UAPs) with an ensemble docking procedure. UAPs are drug-like compounds, which are actual active compounds of a variety of known proteins. The current targets were nine human GPCRs whose three-dimensional (3D) structures are unknown, plus three GPCRs, namely β2-adrenergic receptor (ADRB2), A2A adenosine receptor (A2A), and dopamine D3 receptor (D3), whose 3D structures are known. Homology-based models of the GPCRs were constructed based on the crystal structures with careful sequence inspection. After subsequent molecular dynamics (MD) simulation taking into account the explicit lipid membrane molecules with periodic boundary conditions, we obtained multiple model structures of the GPCRs. For each target structure, docking-screening calculations were carried out via the ensemble docking procedure, using both true active compounds of the target proteins and the UAPs with the multiple target screening (MTS) method. Consequently, the multiple model structures showed various screening results with both poor and high hit ratios, the latter of which could be identified as promising for use in in silico screening to find candidate compounds to interact with the proteins. We found that the hit ratio of true active compounds showed a positive correlation to that of the UAPs. Thus, we could retrieve appropriate target structures from the GPCR models by applying the UAPs, even if no active compound is known for the GPCRs. Namely, the screening result that showed a high hit ratio for the UAPs could be used to identify actual hit compounds for the target GPCRs. © 2011 American Chemical Society. Source

Maruyama Y.,Japan National Institute of Advanced Industrial Science and Technology | Kawamura Y.,AOMi Inc | Nishikawa T.,Hitachi Ltd. | Isogai T.,University of Tokyo | And 2 more authors.
Nucleic Acids Research

The Human Gene and Protein Database (HGPD; http://www.HGPD.jp/) is a unique database that stores information on a set of human Gateway entry clones in addition to protein expression and protein synthesis data. The HGPD was launched in November 2008, and 33 275 human Gateway entry clones have been constructed from the open reading frames (ORFs) of full-length cDNA, thus representing the largest collection in the world. Recently, research objectives have focused on the development of new medicines and the establishment of novel diagnostic methods and medical treatments. And, studies using proteins and protein information, which are closely related to gene function, have been undertaken. For this update, we constructed an additional 9974 human Gateway entry clones, giving a total of 43 249. This set of human Gateway entry clones was named the Human Proteome Expression Resource, known as the 'HuPEX'. In addition, we also classified the clones into 10 groups according to protein function. Moreover, in vivo cellular localization data of proteins for 32 651 human Gateway entry clones were included for retrieval from the HGPD. In 'Information Overview', which presents the search results, the ORF region of each cDNA is now displayed allowing the Gateway entry clones to be searched more easily. © The Author(s) 2011. Published by Oxford University Press. Source

Irei S.,Japan National Institute of Environmental Studies | Irei S.,University of Ryukyus | Takami A.,Japan National Institute of Environmental Studies | Sadanaga Y.,Osaka Prefecture University | And 5 more authors.
Atmospheric Chemistry and Physics

To better understand the secondary air pollution in transboundary air over westernmost Japan, ground-based field measurements of the chemical composition of fine particulate matter ( ≤ ĝ€1ĝ€μm), mixing ratios of trace gas species (CO, O3, NOx, NOy, i-pentane, toluene, and ethyne), and meteorological elements were conducted with a suite of instrumentation. The CO mixing ratio dependence on wind direction showed that there was no significant influence from primary emission sources near the monitoring site, indicating long- and/or mid-range transport of the measured chemical species. Despite the considerably different atmospheric lifetimes of NOy and CO, these mixing ratios were correlated (r2 Combining double low line 0.67). The photochemical age of the pollutants, t[OH] (the reaction time × the mean concentration of OH radical during the atmospheric transport), was calculated from both the NOxĝ€ĝ•ĝ€NOy concentration ratio (NOxĝ€ĝ•ĝ€NOy clock) and the tolueneĝ€ĝ•ĝ€ethyne concentration ratio (hydrocarbon clock). It was found that the tolueneĝ€/ĝ€ethyne concentration ratio was significantly influenced by dilution with background air containing 0.16ĝ€ppbv of ethyne, causing significant bias in the estimation of t[OH]. In contrast, the influence of the reaction of NOx with O3, a potentially biasing reaction channel on [NOx]ĝ€/ĝ€[NOy], was small. The t[OH] values obtained with the NOxĝ€ĝ•ĝ€NOy clock ranged from 2.9ĝ€ × ĝ€105 to 1.3ĝ€ × ĝ€108ĝ€hĝ€moleculeĝ€cmĝ'3 and were compared with the fractional contribution of the mĝ•z 44 signal to the total signal in the organic aerosol mass spectra (f44, a quantitative oxidation indicator of carboxylic acids) and O3 mixing ratio. The comparison of t[OH] with f44 showed evidence for a systematic increase of f44 as t[OH] increased, an indication of secondary organic aerosol (SOA) formation. To a first approximation, the f44 increase rate was (1.05ĝ€±ĝ€0.03)ĝ€ × ĝ€10ĝ'9ĝ€ × ĝ€[OH]ĝ€hĝ'1, which is comparable to the background-corrected increase rate observed during the New England Air Quality Study in summer 2002. The similarity may imply the production of similar SOA component, possibly humic-like substances. Meanwhile, the comparison of t[OH] with O3 mixing ratio showed that there was a strong proportional relationship between O3 mixing ratio and t[OH]. A first approximation gave the increasing rate and background mixing ratio of ozone as (3.48ĝ€±ĝ€0.06)ĝ€ × ĝ€10ĝ'7ĝ€ × ĝ€[OH]ĝ€ppbv hĝ'1 and 30.7ĝ€ppbv, respectively. The information given here can be used for prediction of secondary pollution magnitude in the outflow from the Asian continent. © Author(s) 2016. Source

Toyama Y.,University of Tokyo | Toyama Y.,AOMi Inc | Osawa M.,University of Tokyo | Osawa M.,Keio University | And 3 more authors.
Journal of the American Chemical Society

Chemical exchange processes of proteins on the order of microseconds (μs) to milliseconds (ms) play critical roles in biological functions. Developments in methyl-transverse relaxation optimized spectroscopy (methyl-TROSY), which observes the slowly relaxing multiple quantum (MQ) coherences, have enabled the studies of biologically important large proteins. However, the analyses of μs to ms chemical exchange processes based on the methyl-TROSY principle are still challenging, because the interpretation of the chemical exchange contributions to the MQ relaxation profiles is complicated, as significant chemical shift differences occur in both 1H and 13C nuclei. Here, we report a new methyl-based NMR method for characterizing chemical exchanges, utilizing differential MQ relaxation rates and a heteronuclear double resonance pulse technique. The method enables quantitative evaluations of the chemical exchange processes, in which significant chemical shift differences exist in both the 1H and 13C nuclei. The versatility of the method is demonstrated with the application to KirBac1.1, with an apparent molecular mass of 200 kDa. © 2016 American Chemical Society. Source

Jeon I.,AOMi Inc | Yoon M.,Kangwon National University | Lee J.-H.,Kangwon National University
Applied Optics

Glass bending in LCD displays is an inherent problem that has challenged many engineers. As a solution to this problem, we propose a methodology that can tackle the root of the phenomenon in terms of linear elastic beam theory. Using this hypothesis, we devised a background theory and a solution. In this paper, we present a glass panel to which geometrical changes, such as furrow, groove, and curb have been applied. These geometrical changes are applied to the nonactive area of the glass panel. To confirm the validity of our approach, we conducted simulation tests as well as hands-on experiments to observe the thermo-mechanical behavior of the device under various conditions. The simulation results using the Ansys simulator show that the proposed technique can reduce the deformation level of panel bending by 40%. In the experiment using a bare cell with polarizer films attached and with performing the high temperature reliability test, the deformation level of panel bending is reduced by half compared to the reference glass panel without any geometric alteration. © 2013 Optical Society of America. Source

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