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Abstract

Abstract

This work developed an integrated software named ProKware to present protein structural properties, such as domains, functional sites, families, active sites, binding sites, post-translational modifications, and domain-domain interaction in protein tertiary structures. Using the implemented window-based and web-based interface, users can manipulate and visualize the three-dimensional protein structures, as well as the supported structural properties, which are curated in the back-end protein knowledge base. ProKware demonstrates an effective and convenient way for investigating the protein function and structure relationship.

Overview

The integrated software comprises two main components including protein knowledge base in back tier and a windows-based/web-based application in front tier. Figure 1 depicts the system flow of ProKware. Firstly, the protein knowledge base was constructed to compile protein sequences, protein tertiary structures, and protein structural properties, which were obtained from biological databases available in public domain.

Figure 1. System flow of ProKware.

 

Secondly, the windows-based application in front tier was designed and implemented to present the essential protein structural properties, such as domains, binding sites, and post-translational modification on the protein structural coordinates.

 

Protein Knowledge Base

As given in Table 1, the protein sequences, domain/motifs, protein-protein interacting domains, protein tertiary structures, and post-translational modifications were obtained from Swiss-Prot, InterPro, InterDom, PDB and dbPTM, respectively.

Table 1. The external data sources integrated into the ProKware protein knowledge base.

Knowledge Category

Number of Entries

Database Name

URL

Protein motif1

11,007

InterPro

http://www.ebi.ac.uk/interpro/

Post-translational modifications

786,211

dbPTM2

http://dbptm.mbc.nctu.edu.tw/

Protein tertiary structure

26,260

PDB

http://www.rcsb.org/pdb/

Protein sequence

176,469

Swiss-Prot

http://www.expasy.org/sprot/

Sequence-structure mapping

40,648

UniProt

http://www.pir.uniprot.org/

Protein-protein interacting domains

60,850

InterDom

http://interdom.lit.org.sg/

1This category contains domains, active sites, binding sites, repeats, functional sites and families defined in diverse databases. 2 dbPTM contains totally 14,057 known PTM sites and 772,154 putative PTM sites.

 

Web interface

The website of ProKware’s knowledge base consists of three major searching categories, domain, protein, and PTM.

Domain: When users input an InterPro entry, the software retrieves the general information of this domain, relative PDB file, definitions in different databases and the putative domain-domain interaction of this domain (including the domain name in Pfam and corresponding InterPro entry).

           As shown in Fig. 2, the web interface also contains a button to directly invoke ProKware web-based interface to graphically show the 3D domain structure on web (users need to install our software, ProKware).  The domains within the considered PDB protein structure are highlighted.

Protein: When users input a PDB entry, the software retrieves the Swiss-Prot accession number corresponding to each chain in this PDB file, this protein comes along with its name and its sequence. Software also informs every possible domain and PTM sits within this PDB file and it allow you to observe the structure of these domains by ProKware web-based interface as well.

Figure 2. The embedded software, ProKware web interface ill be invoked when users click on the button. In the blue box, users can adjust the corresponding PDB files and databases.

 

PTM: Searching with PTM is a little different. Users must input the key word of specific PTM, for instance, user can input “phos” to search all related PTM, as shown in Fig. 3, and with the help of ProKware web-based interface, the modified residue of the PTM is capable to be displayed on web.

Figure 3. ProKware web interface supports the visualization of the post-translational modified residues.

 

           If users prefer using other platforms or other visualization software, our web site alternatively provide the script which can be read in by RasMol.

 

Client-end software

ProKware provides an interactive dialog which can be driven by mouse clicks all along the process. As shown in Fig. 4 (a), four scenarios for the investigation of protein structural properties underlying the protein tertiary structures including (1) users can extract a specified protein domain/motif in a specified protein structure; (2) users can retrieve all protein domain/motifs in a specified protein structures; (3) users can extract protein structures that have domains interacted with a specified domain; (4) users can retrieve post-translation modification in a specified protein structure.

The 3-D visualization of protein structural properties along with protein tertiary structures corresponding to users’ selection is in Fig. 4 (a).

           Each of them results in specific presentation, as shown in Fig. 4 (b)..

Figure 4. ProKware windows-based application. (a) User selection of the scenarios of the investigation of protein structural properties including (1) extracting a specified protein domain/motif in a specified protein structure; (2) retrieving all protein domain/motifs in a specified protein structures; (3) extracting protein structures that have domains interacted with a specified domain; (4) retrieving post-translation modification in a specified protein structure. (b) The 3-D visualization of protein structural properties along with protein tertiary structures corresponding to users’ selection in (a).

 

Table 2. Comparation

Unique feature

ProKware

Motif3D

PdbMotif

Description

Direct access

Yes

Yes

 

Connecting the database directly

Database supported

Knowledge base1

PRINTS

PROSITE

Annotation according to specific database

Web-based app.

Yes

Yes

 

Supporting viewing the protein properties on web

Window-based app.

Yes

 

 

Supporting viewing the protein properties of line

RasMol script

Yes

 

Yes

 

Full domain display

Yes

 

 

Capable to display the full definition of all functional sites within specific protein structures

DD interaction display

Yes

 

Capable to display the multiple protein having interaction

PTM sites support

Yes

 

 

Showing the PTM small molecule with PTM sites

Split windows

Yes

 

 

At max 4 separated frames showing diverse contents

Graphic presentation

Rich2

Mono.(Java applet)

By RasMol

3D graphic performance and structure presentation

Motif management

Yes

 

 

Management of different protein with protein properties

Cross platform

Not yet

Yes

Yes

The portability of software

 (Abbrev.: Domain-domain (DD)) 1Swiss-Prot, InterPro, InterDom, PDB and dbPTM. 2ProKware supported cartoon view and strand view to easily verify protein secondary structure. OpenGL pipeline provided efficient viewing performance

References

 

1.             Deshpande, N., Addess, K.J., Bluhm, W.F., Merino-Ott, J.C., Townsend-Merino, W., Zhang, Q., Knezevich, C., Xie, L., Chen, L., Feng, Z. et al. (2005) The RCSB Protein Data Bank: a redesigned query system and relational database based on the mmCIF schema. Nucleic Acids Res, 33, D233-237.

3.             Bateman, A., Coin, L., Durbin, R., Finn, R.D., Hollich, V., Griffiths-Jones, S., Khanna, A., Marshall, M., Moxon, S., Sonnhammer, E.L. et al. (2004) The Pfam protein families database. Nucleic Acids Res, 32, D138-141.

4.             Hulo, N., Sigrist, C.J., Le Saux, V., Langendijk-Genevaux, P.S., Bordoli, L., Gattiker, A., De Castro, E., Bucher, P. and Bairoch, A. (2004) Recent improvements to the PROSITE database. Nucleic Acids Res, 32, D134-137.

5.             Bru, C., Courcelle, E., Carrere, S., Beausse, Y., Dalmar, S. and Kahn, D. (2005) The ProDom database of protein domain families: more emphasis on 3D. Nucleic Acids Res, 33, D212-215.

6.             Mulder, N.J., Apweiler, R., Attwood, T.K., Bairoch, A., Bateman, A., Binns, D., Bradley, P., Bork, P., Bucher, P., Cerutti, L. et al. (2005) InterPro, progress and status in 2005. Nucleic Acids Res, 33, D201-205.

7.             Boeckmann, B., Bairoch, A., Apweiler, R., Blatter, M.C., Estreicher, A., Gasteiger, E., Martin, M.J., Michoud, K., O'Donovan, C., Phan, I. et al. (2003) The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res, 31, 365-370.

8.             Ng, S.K., Zhang, Z., Tan, S.H. and Lin, K. (2003) InterDom: a database of putative interacting protein domains for validating predicted protein interactions and complexes. Nucleic Acids Res, 31, 251-254.

9.             Lee, T.Y., Huang, H.D., Hung, J.H., Huang, H.Y., Yang, Y.S. and Wang, T.H. (2006) dbPTM: an information repository of protein post-translational modification. Nucleic Acids Res, 34, D622-627.

10.          Saqi, M.A. and Sayle, R. (1994) PdbMotif--a tool for the automatic identification and display of motifs in protein structures. Comput Appl Biosci, 10, 545-546.

11.           Gaulton, A. and Attwood, T.K. (2003) Motif3D: Relating protein sequence motifs to 3D structure. Nucleic Acids Res, 31, 3333-3336.

12.           Bairoch, A., Apweiler, R., Wu, C.H., Barker, W.C., Boeckmann, B., Ferro, S., Gasteiger, E., Huang, H., Lopez, R., Magrane, M. et al. (2005) The Universal Protein Resource (UniProt). Nucleic Acids Res, 33, D154-159.

 

About us

Special thanks:

Adviser: Hsien-da Huang

Tech supports: Tzong-yi Lee

Debugger: Wei-chi Wang, Heng-chia Hsin

major developer of this website and ProKware:

Jui-hung Hung, All right reserve 2006

Bid Lab, Institute of Bioinformatics, National Chiao Tung University , Taiwan.
Contact us:bidlab@life.nctu.edu.tw with questions or comments.
Websites:http://ProKware.mbc.nctu.edu.tw/