Enhanced CACTVS browser of the open NCI database

Journal of Chemical Information and Computer Sciences

Volumn 42, Issue 1, 2002, Pages 46-57

  Ihlenfeldt, Wolf dietrich ^b   Voigt, Johannes H ^a,d   Bienfait, Bruno ^a,c   Oellien, Frank ^b   Nicklaus, Marc C ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^c ChemCodes Inc   (United States)

^d MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEX BOOLEAN SEARCHES;

CONFORMATIONS; DATA STRUCTURES; DATABASE SYSTEMS; GRAPHICAL USER INTERFACES; WEB BROWSERS; WORLD WIDE WEB;

MOLECULAR STRUCTURE;

ARTICLE; CHEMICAL STRUCTURE; COMPUTER INTERFACE; FACTUAL DATABASE; HEALTH CARE ORGANIZATION; HUMAN; INTERNET; NEOPLASM; UNITED STATES;

DATABASES, FACTUAL; HUMANS; INTERNET; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NATIONAL INSTITUTES OF HEALTH (U.S.); NEOPLASMS; UNITED STATES; USER-COMPUTER INTERFACE;

EID: 0036025426     PISSN: 00952338     EISSN: None     Source Type: Journal    
DOI: 10.1021/ci010056s     Document Type: Article

References (30)

1. Voigt, J.H.; Bienfait, B.; Wang, S.; Nicklaus, M.C. Comparison of the NCI Open Database With Seven Large Chemical Structural Databases. J. Chem. Inf, Comput. Sci. 2001, 41, 702-712.
2. http://dtp.nci.nih.gov.
3. Milne, G.W.A.; Miller, J.A. The NCI Drug Information System. 1. System Overview. J. Chem. Inf. Comput. Sci. 1986, 26, 154-159.
4. Milne, G.W.A.; Feldman, A.; Miller, J.A.; Daly, G.P.; Hammel, M.J. The NCI Drug Information System. 2. DIS Pre-Registry. J. Chem. Inf. Comput. Sci. 1986, 26, 159-168.
5. Milne, G.W.A.; Feldman, A.; Miller, J.A.; Daly, G.P. The NCI Drug Information System. 3. The DIS Chemistry Module. J. Chem. Inf. Comput. Sci. 1986, 26, 168-179.
6. Milne, G.W.A.; Miller, J.A.; Hoover, J.R. The NCI Drug Information System. 4. Inventory and Shipping Modules. J. Chem. Inf. Comput. Sci. 1986, 26, 179-185.
7. Zehnacker, M.T.; Brennan, R.H.; Milne, G.W.A.; Miller, J.A. The NCI Drug Information System. 5. DIS Biology Module. J. Chem. Inf. Comput. Sci. 1986, 26, 186-193.
8. Zehnacker, M.T.; Brennan, R.H.; Milne, G.W.A.; Miller, J.A.; Hammel, M.J. The NCI Drug Information System. 6. System Maintenance. J. Chem. Inf. Comput. Sci. 1986, 26, 193-197.
9. http://dtp.nci.nih.gov/docs/dtp_data.html.
10. Limited search capabilities in subsets of the NCI database are available at DTP's Web site, at http://dtp.nci.nih.gov/docs/dtp_search.html.
11. Dalby, A.; Nourse, J.G.; Hounshell, W.D.; Gnshurst, A.K.I.; Grier, D.L.; Leland, B.A.; Laufer, J. Description of Several Chemical-Structure File Formats Used by Computer-Programs Developed at MOLECULAR DESIGN LIMITED. J. Chem. Inf. Comput. Sci. 1992, 32, 244-255.
12. http://dtp.nci.nih.gov/webdata.html.
13. http://129.43.27.140/ncidb2/download.html.
14. Ihlenfeldt, W.D.; Takahashi, Y.; Abe, S.; Sasaki, S. Computation and Management of Chemical Properties in CACTVS: An Extensible Networked Approach Toward Modularity- and Flexibility. J. Chem. Inf. Comput. Sci. 1994, 34, 109-116.
15. A comparison in tabular format of structure-based, searchable, smallmolecule databases on the World Wide Web has been posted on our server at http://cactus.nci.nih.gov/ncidb2/chem_www.html.
16. Should the URLs be found not to be valid any more, please contact the authors.
17. http://dtp.nci.nih.gov/docs/cancer/cancer_data.html.
18. http://dtp.nci.nih.gov/docs/aids/aids_data.html.
19. Weininger, D. SMILES, A Chemical Language and Information-System 0.1. Introduction to Methodology and Encoding Rules. J. Chem. Inf. Comput. Sci. 1988, 28, 31-36.
20. Weininger, D.; Weininger, A.; Weininger, J.L. SMILES. 2. Algorithm for Generation of Unique SMILES Notation. J. Chem. Inf. Comput. Sci. 1989, 29, 97-101.
21. Private communication from Daylight Chemical Information Systems, Inc.
22. http://www2.ccc.uni-erlangen.de/software/corina.
23. Sadowski, J.; Rudolph, C.; Gasteiger, J. The Generation of 3D-Models of Host-Guest Complexes. Anal. Chim. Acta 1992, 265, 233-241.
24. Poroikov, V.V.; Filimonov, D.A.; Budunova, A.P. Comparison of Results of Prediction of a Spectrum of Biological-Activity of Chemical-Compounds by PASS Computer-System and by the Experts. Nauchno-Tekhnicheskaya Informatsiya Seriya 2 Informatsionnye Protsessy I Sistemy 1993, 11-13.
25. Mannhold, R.; Dross, K. Calculation Procedures for Molecular Lipophilicity: a Comparative Study. Quant. Struct. Act. Relat. 1996, 15, 403-409.
26. http://www2.ccc.uni-erlangen.de/software/cactvs/index.html.
27. Tool Command Language, an easily extendable scripting language; see, e.g., Osterhout, J.K. Tcl and the TK Toolkit; Addison-Wesley: ISBN 020163337X.
28. The principal deployment platforms for the service at the time of this writing are GNU/Linux at the LMC and IRIX at the Computer Chemistry Center. Extending the CACTVS file handling for large files with 64-bit positioning and size was straightforward on IRIX with the XFS file system but necessitated quite a hit of patching on Linux. First, we had to use an inofficial prerelease Linux 2.4 kernel in order to obtain the necessary basic operating system support for files larger than 2GB. At the time of this work, semifunctional patches to provide the large file support (LFS) were available in the experimental kernel which is part of the SuSE 7.0 Linux distribution. Nevertheless, while the basic Ext2 file system with large file support worked more or less as expected, many operating system support routines, such as quotas, limit checks, etc. were found to not yet have been properly adapted. For example, we were unable to actually write files larger than 2GB except as root user. For the production of the database this was acceptable. However, to be able to read these large files as a nonroot user on a system which was configured to be reasonably secure, a small kernel patch had to be developed. Additionally, the C runtime library- was found to contain a number of errors with respect to handling large files, which had to be circumvented. For example, the ftel164() function in the distributed C runtime library, needed to determine the current file I/O position, returned negative values when the file was positioned beyond the 2GB position, despite setting the appropriate compilation flags to activate the LFS execution environment. Even after solution of these problems, retrieval of individual structure records was initially found to be very slow and dramatically increasing in latency with increasing offset from the database file beginning [higher NSC/record numbers]. It turned out that the performance of the system call mmap64(), which affects memory paging, is much less optimized in early 2.4 kernel versions of Linux when compared with, e.g., IRIX/XFS. A workaround for this problem was achieved by certain changes in the format of the database file. The retrieval speeds on the Linux and the IRIX servers are now very similar and are typically in the 1-s range for any NSC number. It is hoped that future versions of Linux will solve these problems on the operating system level.
29. Nicklaus, M.C.; Neamati, N.; Hong, H.; Mazumder, A.; Sunder, S.; Chen, J.; Milne, G.W.; Pommier, Y. HIV-1 Integrase Pharmacophore: Discovery of Inhibitors Through Three-Dimensional Database Searching. J. Med. Chem. 1997, 40, 920-929.
30. A file at URL ftp://dtpsearch.ncifcrf.gov/dec01_2d.bin, available on the DTP web page http://dtp.nci.nih.gov/docs/3d_database/structural_information/structural_data.h tml.