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 | Year: 2011
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.
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 | Year: 2012
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.
Gando G.,AOMi Inc |
Yamada T.,Panasonic |
Sato H.,Hokkai Gakuen University |
Oyama S.,Hokkaido University |
Kurihara M.,Hokkaido University
Expert Systems with Applications | Year: 2016
Systems for aggregating illustrations require a function for automatically distinguishing illustrations from photographs as they crawl the network to collect images. A previous attempt to implement this functionality by designing basic features that were deemed useful for classification achieved an accuracy of only about 58%. On the other hand, deep neural networks had been successful in computer vision tasks, and convolutional neural networks (CNNs) had performed good at extracting such useful image features automatically. We evaluated alternative methods to implement this classification functionality with focus on deep neural networks. As the result of experiments, the method that fine-tuned deep convolutional neural network (DCNN) acquired 96.8% accuracy, outperforming the other models including the custom CNN models that were trained from scratch. We conclude that DCNN with fine-tuning is the best method for implementing a function for automatically distinguishing illustrations from photographs. © 2016 Elsevier Ltd
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 | Year: 2016
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.
Handa N.,Shinshushinmachi Fossil Museum |
Nakada K.,Josai University |
Anso J.,AOMi Inc |
Matsuoka A.,Niigata University
Newsletters on Stratigraphy | Year: 2014
The definition of the Global Boundary Stratotype Section and Point (GSSP) of the Bathonian/ Callovian (Middle Jurassic) boundary is under debate in Europe. The sections that include the Bathonian/ Callovian boundary are still limited in East Asia. In Japan, the Middle Jurassic Kaizara Formation, which is located within the Tetori Group, is exposed in Fukui Prefecture, central Japan. This formation contains abundant ammonite fossils. On the basis of ammonite fossils, the Kaizara Formation has been assigned to the late Bathonian to early Callovian age. Therefore, the Kaizara Formation is an important formation encompassing the Bathonian/Callovian boundary in East Asia. However, the fossil-bearing horizons have not been observed clearly in previous studies. In the present study, a detailed analysis of the molluscan fossil-bearing horizons of the Kaizara Formation was conducted utilizing three stratigraphic successions. On the basis of seven identified genera and nine species of ammonites, the presence of three successive assemblage zones first proposed by a previous study is confirmed: the Pseudoneuqueniceras yokoyamai, the Kepplerites japonicus, and the Oxycerites assemblage zones. Of these, the Pseudoneuqueniceras yokoyamai Assemblage Zone was assumed to correspond to the Orbis- Oppeli Zone (late Bathonian), and the Kepplerites assemblage Zone was assumed to be comparable to the early Callovian age. These results indicate that the Bathonian/Callovian boundary lies within the middle part of the Kaizara Formation. © 2014 Gebrüder Borntraeger, Stuttgart, Germany.
Ono K.,AOMi Inc |
Ono K.,Japan National Institute of Advanced Industrial Science and Technology |
Ueda H.,AOMi Inc |
Yoshizawa Y.,AOMi Inc |
And 5 more authors.
Journal of Medicinal Chemistry | Year: 2010
GPVI is a key receptor for collagen-induced platelet activation. Loss or inhibition of GPVI causes only mildly prolonged bleeding times but prevents arterial thrombus formation in animal models. Therefore, GPVI is considered to be a potent target molecule for therapy of thrombotic diseases. Recently, it was reported that the AT1-receptor antagonist losartan (DuP-753) and EXP3179 inhibit platelet adhesion and aggregation via GPVI. However, it is still not clear how losartan is associated with inhibition of binding between GPVI and collagen at the molecular level. Here, we show by NMR that losartan directly interacts with the hydrophobic region consisting of strands C and E in the N-terminal Ig-like domain of GPVI. A reliable GPVI-losartan complex model is presented by using a combination of NMR data and in silico tools. These data indicated that the phenyl group with the tetrazole ring in losartan plays a crucial role in the interaction with GPVI. © 2010 American Chemical Society.
Jeon I.,AOMi Inc |
Yoon M.,Kangwon National University |
Lee J.-H.,Kangwon National University
Applied Optics | Year: 2013
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.
Sugiki T.,AOMi Inc |
Sugiki T.,Japan National Institute of Advanced Industrial Science and Technology |
Takahashi H.,Japan National Institute of Advanced Industrial Science and Technology |
Nagasu M.,AOMi Inc |
And 3 more authors.
Analytical Biochemistry | Year: 2010
Intracellular lipid translocation is mediated by lipid transfer proteins and their functional impairments cause severe disorder in lipid metabolism. However, molecular mechanisms of protein-mediated lipid transfer remain unclear since conventional assay methods could not observe elementary processes in the lipid transfer reaction, such as lipid bilayer binding and lipid uptake. In this study, we found that ceramide extraction mediated by a ceramide trafficking protein (CERT) could be detected as decreasing the response of surface plasmon resonance (SPR). Based on this finding, we developed a novel real-time assay method that enables quantitative evaluation of the ceramide extraction activity of CERT, using the SPR technique. Performing this SPR-based assay using ceramide-embedded and ceramide-free lipid bilayers as ligands allows for the exclusive investigation of ceramide uptake processes, differentiating them from other CERT-membrane binding events. Furthermore, mutagenesis experiments of CERT using this SPR-based assay clearly elucidated whether an amino acid residue plays a role in the ceramide uptake process or the lipid bilayer binding process. This SPR-based assay method can separately evaluate the lipid extraction activity and lipid bilayer binding activity of the lipid transfer proteins, and provide more detailed information about lipid transfer phenomena. © 2009 Elsevier Inc. All rights reserved.
PubMed | Japan National Institute of Advanced Industrial Science and Technology, Osaka University and AOMi Inc
Type: Journal Article | Journal: Journal of chemical theory and computation | Year: 2015
A molecular dynamics (MD) simulation program for biological macromolecules was implemented with a non-Ewald scheme for long-ranged electrostatic interactions and run on a general purpose graphics processing unit (GPU). We recently developed several non-Ewald methods to compute the electrostatic energies with high precision. In particular, the zero-dipole summation (ZD) method, which takes into account the neutralities of charges and dipoles in a truncated subset, enables the calculation of electrostatic interactions with high accuracy and low computational cost, and its algorithm is simple enough to be implemented in a GPU. We developed an MD program with the space decomposition algorithm, myPresto/psygene, and applied it to several biological macromolecular systems with GPUs implementing the ZD method. Rapid computing performance with high accuracy was obtained.