Nucleic Acids Research, 2003, Vol. 31, No. 13 3400-3403
© 2003 Oxford University Press
NRSAS: Nuclear Receptor Structure Analysis Servers
Emmanuel Bettler,
Roland Krause1,
Florence Horn2 and
Gert Vriend*
CMBI KUN, PO Box 9010, 6500 GL Nijmegen, The Netherlands
1 Washington University, Center for Computational Mechanics, Saint Louis, MO, USA
2 UCSF, Genentech Hall, 600 16th Street, San Francisco CA 94143-2240, USA
*To whom correspondence should be addressed. Tel: +31 24 36 53391; Fax: +31 24 36 52977; Email: vriend{at}cmbi.kun.nl
Received February 15, 2003; Accepted March 4, 2003
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ABSTRACT
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We present a coherent series of servers that can perform a large
number of structure analyses on nuclear hormone receptors. These
servers are part of the NucleaRDB project, which provides a
powerful information system for nuclear hormone receptors. The
computations performed by the servers include homology modelling,
structure validation, calculating contacts, accessibility values,
hydrogen bonding patterns, predicting mutations and a host of
two- and three-dimensional visualisations. The Nuclear Receptor
Structure Analysis Servers (NRSAS) are freely accessible at
http://www.cmbi.kun.nl/NR/servers/html/ and in-house copies
can be obtained upon request.
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INTRODUCTION
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Complicated data analysis tools are rapidly becoming an integral
aspect of work in most bioscience laboratories. Unfortunately,
many tools are expensive, difficult to install or use, require
special hardware or are otherwise not easily accessible to scientists.
The World Wide Web (WWW) is a good solution for this problem.
Specialists can maintain WWW-based servers in laboratories that
have adequate hardware, software and expertise available, while
the scientists only have to concentrate on the scientific aspects
of servers.
Nuclear hormone receptors (NRs) are becoming a very important topic for the pharmaceutical industry, which is spurring a flurry of activities. The NucleaRDB (1) was set up to gather, combine and disseminate information on NRs. This information system integrates sequence data, mutation data, ligand binding data and three-dimensional structures to form a one-stop-shopping-centre for NR-related information.
WHAT IF (2) is a versatile program for the analysis, manipulation, prediction and visualisation of macromolecular structures as stored in the PDB (3) databank. This program is very widely used, in particular by research groups interested in different aspects of protein structure analysis. Unfortunately, the large number of options and commands that WHAT IF offers makes it difficult to use and limits its applicability. This is a problem for laboratories that only occasionally need to analyse protein structures. We have solved this problem for the users of the NucleaRDB by producing a series of WWW-based servers that can run many WHAT IF options on nuclear receptor structures.
Table 1 lists some of the options that can be performed by the Nuclear Receptor Structure Analysis Servers (NRSAS). Figure 1 shows the WWW page for a typical server. The NRSAS are freely available at http://www.cmbi.kun.nl/NR/servers/html/.
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Figure 1. NRSAS input screenshot. The right frame is the input form of the server that calculates protein–ligand interactions. The pull-down menu with 17 representative nuclear receptor related PDB files is activated. The left frame lists all 19 classes of options. (See Fig. 2 for the result of activating this server.)
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STRUCTURE AND USE OF SERVERS
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All the servers, input forms, result pages, and so on, are produced
by a python script. This script reads a meta-file in which the
server manager describes in English the tasks the server should
execute. This meta-file also contains the help texts and explanations
for all the input and output forms and tables. A script for
the program WHAT IF forms the most complicated part of the meta-file.
This script contains all the WHAT IF commands a user would have
typed in an interactive session. File names, residue ranges,
and so on, have to be indicated by the user. The server builder
therefore knows a series of commands that it can extract from
the WHAT IF script, and converts it into input boxes in the
WWW input form. Upon execution, the values typed by the user
in those input boxes will be inserted in the WHAT IF script.
This generates a valid WHAT IF script that performs the desired
option with no need for the user to understand the script language
and the interactive options of WHAT IF.
It is therefore possible to make one's own WHAT IF based servers. Only a WHAT IF license and the python scripts to build and maintain the servers are needed. A basic understanding of the WHAT IF software to write WHAT IF scripts is also required. Python (1.5 or higher), WHAT IF and an HTTP server (e.g. Apache) have to be installed prior to setting up and running the servers. Installation notes and other information are available via the WWW pages for the servers.
Figure 1 shows a screenshot of a typical server page. This server lists the contacts between the protein and ligands. Figure 2 shows a screenshot of the output obtained a few seconds after submitting the job prepared in Figure 1.
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Figure 2. NRSAS output screenshot. The left frame lists all 19 classes of options. The right frame shows the results of the server run, as illustrated in Figure 1. From left to right the residue number, residue type, PDB identifier of residue, chain identifier and name of atom making the contact are indicated. The left five columns are for the atom of the macromolecule; the next five columns are for the atom of the ligand. The right column gives the inter-atomic distance in Ångstrom.
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It takes about 30 seconds to build 100 servers. We therefore
do not provide options to add or delete servers. Servers are
updated by editing the server meta-file and running the server
generation script again. Figure
3 shows the part of the meta-file
needed by the server shown in Figures
1 and
2.
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Figure 3. Section of the meta-file used to build the server illustrated in Figures 1 and 2. Most data can easily be correlated to the content of the forms in Figures 1 and 2. The input record sets up the chooser for nuclear receptor PDB files. The six lines that start with ‘getmol’ correspond to a WHAT IF script.
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We believe that this concept of servers for molecular class
specific protein structure analysis will be useful for scientists
who like to have occasional access to such software but lack
the time, money, software, hardware or human infrastructure
to maintain such facilities in their laboratory.
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ACKNOWLEDGEMENTS
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The authors thank their colleagues at the CMBI, Organon and
Unilever for stimulating discussions. Rob Hooft and Jens Nielsen
provided valuable technical support. This project was supported
by LionBiosciences Ag in Heidelberg, Germany.
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REFERENCES
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- Horn,F., Vriend,G. and Cohen,F.E. (2001) Collecting and harvesting biological data: the GPCRDB and NucleaRDB information systems. Nucleic Acids Res., 29, 346–349.[Abstract/Free Full Text]
- Vriend,G. (1990) WHAT IF: a molecular modelling and drug design program. J. Mol. Graph., 8, 52–56.[CrossRef][Web of Science][Medline]
- Bernstein,F.C., Koetzle,T.F., Williams,G.J.B., Meyer,E.F.,Jr, Brice,M.D., Rogers,J.R., Kennard,O., Shimanouchi,T. and Tasumi,M. (1977) The Protein Data Bank: a computer-based archival file for macromolecular structures. J. Mol. Biol., 112, 535–542.[Web of Science][Medline]
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