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Research paper : Advanced in-silico drug screening to achieve high hit ratio (Y. Fukunishi et al.)−70−Synthesiology - English edition Vol.2 No.1 (2009) our research, to distribute our package, but not to negotiate with reagent vendors. Collaboration with private corporations is being promoted through the encouragement of industry-government-academia coordination, however, and this issue is therefore also considered to be a future task.AcknowledgementThis study was supported by the New Energy and Industrial Technology Development Organization (NEDO) and the Ministry of Economy, Trade and Industry (METI) of Japan.TerminologyProtein-compound docking software: Software that computationally predicts the most feasible and energetically stable structure of protein-compound complexes by allocating a compound adjacent to the surface of a 3D protein structure. The docking simulation takes several seconds to a minute in drug screening. Typical software includes DOCK, AutoDock, and myPresto.Docking scores: Values that represent the strength of a protein-compound interaction estimated by docking software, and generally correspond to the free energy of binding.Enrichment: The ratio of the number of correct hit compounds to the number of candidate compounds predicted by computations in drug screening. In general, one out of 10,000 compounds hit in a random screening; thus, if one out of 100 compounds predicted by computational analysis was found to be a hit compound, the enrichment with respect to the random experiment would be 100-fold.Term 1.Term 2.Term 3.References[1][2][3][4][5][6][7][8][9][10]http://www.mdl.com/jp/products/experiment/cims/index.jsp http://www.molecular-networks.com/software/corina/index.htmlM. Hattori, Y. Okuno, S. Goto and M. Kanahisa: Development of a chemical structure comparison method for integrated analysis of chemical and genomic information in the metabolic pathways. J. Am. Chem. Soc., 125 (39), 11853-65 (2003).J. Gasteiger and T. Engel: Chemoinformatics: A textbook. WILEY-VCH: Weinheim. (2003).http://www.lmcp.jussieu.fr/sincris-top/logiciel/prg-babel.htmlhttp://openbabel.org/wiki/Main_PageJ. Wang, R. M. Wolf, J. W. Caldwell, P. A. Kollman and D. A. Case: Development and testing of a general amber force field. J. Compt. Chem., 25 (9), 1157-1174 (2004).http://www.ccdc.cam.ac.uk/products/csd/Y. Fukunishi, Y. Mikami and H. Nakamura: The filling potential method: A method for estimating the free energy surface for protein-ligand docking. J. Phys. Chem. B. 107 (47), 13201-13210 (2003).J. Gasteiger and M. Marsili: A new model for calculating atomic [11][12][13][14][15][16][17][18][19][20]charges in molecules. Tetrahedron Lett., 3181-3184 (1978).http://openmopac.net/index.htmlJ. Wang, P. Cieplak and P.A. Kollman: How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? J. Comput. Chem., 21 (12), 1049-1074 (2000).Y. Fukunishi, Y. Mikami and H. Nakamura: Similarities among receptor pockets and among compounds: Analysis and application to in silico ligand screening. J. Mol. Graph. and Model., 24 (1), 34-45 (2005).Y. Fukunishi, Y. Mikami, K. Takedomi, M. Yamanouchi, H. Shima and H. Nakamura: Classification of chemical compounds by protein-compound docking for use in designing a focused library. J. Med. Chem., 49 (2), 523-533 (2006).Y. Fukunishi, Y. Mikami, S. Kubota and H. Nakamura: Multiple target screening method for robust and accurate in silico ligand screening. J. Mol. Graph. and Model. 25 (1), 61-70 (2005).Y. Fukunishi, S. Kubota and H. Nakamura: Noise reduction method for molecular interaction energy: application to in silico drug screening and in silico target protein screening. J. Chem. Info. Mod., 46 (5), 2071-2084 (2006).Y. Fukunishi, S. Hojo and H. Nakamura: An efficient in silico screening method based on the protein-compound affinity matrix and its application to the design of a focused library for cytochrome P450 (CYP) ligands. J. Chem. Info. Mod., 46 (6), 2610-2622 (2006).http://presto.protein.osaka-u.ac.jp/myPresto4/index_e.htmlhttp://presto.protein.osaka-u.ac.jp/LigandBox/web_search.cgiJ. J. Irwin and B. K. Shoichet: ZINC–a free database of commercially available compounds for virtual screening. J. Chem. Inf. Model., 45 (1), 177-82 (2005).AuthorsYoshifumi FukunishiDr. Fukunishi received his Ph.D. from the Graduate School of Engineering, Kyoto University, in 1994 and served as an adjunct researcher at the National Institute for Advanced Interdisciplinary Research, Ministry of International Trade and Industry (MITI). He then worked as an HFSP fellow, a post-doctoral researcher at Rutgers University, a JST post-doctoral fellow at RIKEN, and at Hitachi, Ltd., and has held the position of senior research scientist at the Biomedicinal Information Research Center (BIRC), AIST, since 2000. He specializes in computational chemistry and was in charge of developing prototype models, devising algorithms, and designing the overall research in this studyYuusuke SugiharaMr. Sugihara received his M.S. from the Macromolecular Chemistry Course, Department of Chemistry, Graduate School of Science, Hiroshima University, in 1996, and joined Arakawa Chemical Industries, Ltd. in the same year. After leaving that company in 2000, he joined Fujitsu Kyushu System Engineering, Limited in 2001. He was primarily in charge of developing 3D structures from cataloged compounds in this study.Yoshiaki MikamiMr. Mikami joined Hitachi East Japan Solutions, Ltd. in 1987 and is currently engaged in system development in such areas

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