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iScreen: world’s first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan

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Abstract

The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user’s interest. iScreen is the world’s first web server that employs world’s largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

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References

  1. Chen CY, Chen CYC (2010) Insights into designing the dual-targeted HER2/HSP90 inhibitors. J Mol Graphics Model 29(1):21–31

    Article  Google Scholar 

  2. Chang TT, Huang HJ, Lee KJ, Yu HW, Chen HY, Tsai FJ, Sun MF, Chen CY (2010) Key features for designing phosphodiesterase-5 inhibitors. J Biomol Struct Dyn 28(3):309–321

    CAS  Google Scholar 

  3. Chen CY, Huang HJ, Tsai FJ, Chen CYC (2010) Drug design for Influenza A virus subtype H1N1. J Taiwan Inst Chem Eng 41(1):8–15

    Article  CAS  Google Scholar 

  4. Chen CYC (2010) Virtual screening and drug design for PDE-5 receptor from traditional chinese medicine database. J Biomol Struct Dyn 27(5):627–640

    CAS  Google Scholar 

  5. Chen CYC (2009) Chemoinformatics and pharmacoinformatics approach for exploring the GABA-A agonist from Chinese herb suanzaoren. J Taiwan Inst Chem Eng 40(1):36–47

    Article  CAS  Google Scholar 

  6. Chen CYC (2009) Computational screening and design of traditional Chinese medicine (TCM) to block phosphodiesterase-5. J Mol Graphics Model 28(4):261–269

    Google Scholar 

  7. Chen KC, Chen CYC (2011) Stroke Prevention by traditional Chinese medicine? A genetic algorithm, support vector machine and molecular dynamics approach. Soft Matter 7(8):4001–4008

    Article  CAS  Google Scholar 

  8. Chen CYC (2011) TCM Database@Taiwan: the world’s largest traditional chinese medicine database for drug screening in silico. PLoS One 6(1):e15939

    Article  CAS  Google Scholar 

  9. Korb O, Stutzle T, Exner TE (2009) Empirical scoring functions for advanced protein-ligand docking with PLANTS. J Chem Inf Model 49(1):84–96

    Article  CAS  Google Scholar 

  10. Jones G, Willett P, Glen RC (1995) Molecular recognition of receptor sites using a genetic algorithm with a description of desolvation. J Mol Biol 245(1):43–53

    Article  CAS  Google Scholar 

  11. Jones G, Willett P, Glen RC, Leach AR, Taylor R (1997) Development and validation of a genetic algorithm for flexible docking. J Mol Biol 267(3):727–748

    Article  CAS  Google Scholar 

  12. Irwin JJ, Shoichet BK, Mysinger MM, Huang N, Colizzi F, Wassam P, Cao Y (2009) Automated docking screens: a feasibility study. J Med Chem 52(18):5712–5720

    Article  CAS  Google Scholar 

  13. Douguet D, Munier-Lehmann H, Labesse G, Pochet S (2005) LEA3D: a computer-aided ligand design for structure-based drug design. J Med Chem 48(7):2457–2468

    Article  CAS  Google Scholar 

  14. Wass MN, Kelley LA, Sternberg MJ (2010) 3DLigandSite: predicting ligand-binding sites using similar structures. Nucleic Acids Res 38(Web Server issue):W469–W473

    Article  CAS  Google Scholar 

  15. Liu X, Ouyang S, Yu B, Liu Y, Huang K, Gong J, Zheng S, Li Z, Li H, Jiang H (2010) PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach. Nucleic Acids Res 38(Web Server issue):W609–W614

    Article  CAS  Google Scholar 

  16. Dey F, Caflisch A (2008) Fragment-based de novo ligand design by multiobjective evolutionary optimization. J Chem Inf Model 48(3):679–690

    Article  CAS  Google Scholar 

  17. Law JMS, Fung DYK, Zsoldos Z, Simon A, Szabo Z, Csizmadia IG, Johnson AP (2003) Validation of the SPROUT de novo design program. Theochem-J Mol Struct 666:651–657

    Article  Google Scholar 

  18. Danziger DJ, Dean PM (1989) Automated site-directed drug design: the prediction and observation of ligand point positions at hydrogen-bonding regions on protein surfaces. Proc R Soc Lond B Biol Sci 236(1283):115–124

    Article  CAS  Google Scholar 

  19. Nishibata Y, Itai A (1993) Confirmation of usefulness of a structure construction program based on three-dimensional receptor structure for rational lead generation. J Med Chem 36(20):2921–2928

    Article  CAS  Google Scholar 

  20. Murray CW, Clark DE, Byrne DG (1995) PRO_LIGAND: an approach to de novo molecular design. 6. Flexible fitting in the design of peptides. J Comput-Aided Mol Des 9(5):381–395

    Article  CAS  Google Scholar 

  21. Rotstein SH, Murcko MA (1993) GenStar: a method for de novo drug design. J Comput-Aided Mol Des 7(1):23–43

    Article  CAS  Google Scholar 

  22. Bohm HJ (1992) The computer program LUDI: a new method for the de novo design of enzyme inhibitors. J Comput-Aided Mol Des 6(1):61–78

    Article  CAS  Google Scholar 

  23. Roe DC, Kuntz ID (1995) BUILDER v.2: improving the chemistry of a de novo design strategy. J Comput-Aided Mol Des 9(3):269–282

    Article  CAS  Google Scholar 

  24. Pearlman DA, Murcko MA (1996) CONCERTS: dynamic connection of fragments as an approach to de novo ligand design. J Med Chem 39(8):1651–1663

    Article  CAS  Google Scholar 

  25. Vinkers HM, de Jonge MR, Daeyaert FF, Heeres J, Koymans LM, van Lenthe JH, Lewi PJ, Timmerman H, Van Aken K, Janssen PA (2003) SYNOPSIS: synthesize and optimize system in silico. J Med Chem 46(13):2765–2773

    Article  CAS  Google Scholar 

  26. Brown N, McKay B, Gilardoni F, Gasteiger J (2004) A graph-based genetic algorithm and its application to the multiobjective evolution of median molecules. J Chem Inf Comput Sci 44(3):1079–1087

    CAS  Google Scholar 

  27. Chen G, Li S (1992) Ben cao gang mu tong shi = general explanation of compendium of materia medica. Xue yuan chu ban she, Beijing Shi

    Google Scholar 

  28. Fang Y, Zhang Z, Miao X (1991) Shang han lun tiao bian, Shanghai gu ji chu ban she : Xin hua shu dian Shanghai fa xing suo fa xing, Shanghai

  29. Lü X (2002) Zhong yao jian bie da quan. Hunan ke xue ji shu chu ban she, Changsha Shi

  30. Miao X, Zheng J (2002) Shennong ben cao jing shu. Zhong yi gu ji chu ban she, Beijing

    Google Scholar 

  31. Nanjing Zhong yi yao da xue, Zhao G, Dai S, Chen R (2006) Zhong yao da ci dian. Shanghai ke xue ji shu chu ban she, Shanghai

  32. Sayers EW, Barrett T, Benson DA, Bolton E, Bryant SH, Canese K, Chetvernin V, Church DM, DiCuccio M, Federhen S, Feolo M, Geer LY, Helmberg W, Kapustin Y, Landsman D, Lipman DJ, Lu ZY, Madden TL, Madej T, Maglott DR, Marchler-Bauer A, Miller V, Mizrachi I, Ostell J, Panchenko A, Pruitt KD, Schuler GD, Sequeira E, Sherry ST, Shumway M, Sirotkin K, Slotta D, Souvorov A, Starchenko G, Tatusova TA, Wagner L, Wang YL, Wilbur WJ, Yaschenko E, Ye J (2010) Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 38:D5–D16

    Article  CAS  Google Scholar 

  33. Clark M (1998) The ISI web of science. Abstracts of Papers of the American Chemical Society 216:U525

    Google Scholar 

  34. Gunda T (2007) ChemBioOffice. Chem World 4(11):70

    Google Scholar 

  35. Karzazi Y, Surpateanu G (1999) An empirical MM2 augmented force field for the cycloimmonium ylides. J Mol Struct 510(1–3):197–205

    Article  CAS  Google Scholar 

  36. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Del Rev 46(1–3):3–26

    Article  CAS  Google Scholar 

  37. Gordon JC, Myers JB, Folta T, Shoja V, Heath LS, Onufriev A (2005) H ++: a server for estimating pKas and adding missing hydrogens to macromolecules. Nucleic Acids Res 33(Web Server issue):W368–W371

    Article  CAS  Google Scholar 

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Acknowledgments

The research was supported by grants from the National Science Council of Taiwan (NSC 99-2221-E-039-013-), Committee on Chinese Medicine and Pharmacy (CCMP100-RD-030) China Medical University and Asia University (CMU99-TCM, CMU99-S-02, CMU99-ASIA-25, CMU99-ASIA-26 CMU99-ASIA-27 CMU99-ASIA-28). This study is also supported in part by Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH100-TD-B-111-004) and Taiwan Department of Health Cancer Research Center of Excellence (DOH100-TD-C-111-005). We are grateful to the Asia University cloud-computing facilities.

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Authors and Affiliations

  1. Laboratory of Computational and Systems Biology, School of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan

    Tsung-Ying Tsai, Kai-Wei Chang & Calvin Yu-Chian Chen

  2. Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA

    Calvin Yu-Chian Chen

  3. Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Calvin Yu-Chian Chen

Authors
  1. Tsung-Ying Tsai
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  2. Kai-Wei Chang
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  3. Calvin Yu-Chian Chen
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Correspondence to Calvin Yu-Chian Chen.

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Tsai, TY., Chang, KW. & Chen, C.YC. iScreen: world’s first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan . J Comput Aided Mol Des 25, 525–531 (2011). https://doi.org/10.1007/s10822-011-9438-9

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  • DOI: https://doi.org/10.1007/s10822-011-9438-9

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