BUDDY-system: A web site for constructing a dataset of protein pairs between ligand-bound and unbound states
© Morita et al; licensee BioMed Central Ltd. 2011
Received: 21 December 2010
Accepted: 22 May 2011
Published: 22 May 2011
Elucidating molecular recognition by proteins, such as in enzyme-substrate and receptor-ligand interactions, is a key to understanding biological phenomena. To delineate these protein interactions, it is important to perform structural bioinformatics studies relevant to molecular recognition. Such studies require a dataset of protein structure pairs between ligand-bound and unbound states. In many studies, the same well-designed and high-quality dataset has been used repeatedly, which has spurred the development of subsequent relevant research. Using previously constructed datasets, researchers are able to fairly compare obtained results with those of other studies; in addition, much effort and time is saved. Therefore, it is important to construct a refined dataset that will appeal to many researchers. However, constructing such datasets is not a trivial task.
We have developed the BUDDY-system, a web site designed to support the building of a dataset comprising pairs of protein structures between ligand-bound and unbound states, which are widely used in various areas associated with molecular recognition. In addition to constructing a dataset, the BUDDY-system also allows the user to search for ligand-bound protein structures by its unbound state or by its ligand; and to search for ligands by a particular receptor protein.
The BUDDY-system receives input from the user as a single entry or a dataset consisting of a list of ligand-bound state protein structures, unbound state protein structures, or ligands and returns to the user a list of protein structure pairs between the ligand-bound and the corresponding unbound states. This web site is designed for researchers who are involved not only in structural bioinformatics but also in experimental studies. The BUDDY-system is freely available on the web.
We plan to implement more advanced search options in the future, such as protein sequence similarity search and chemical structure search from SMILES.
Summary of the results obtained using the BUDDY-system against various datasets
Availability and Requirements
The BUDDY-system is freely available at URL http://www.bi.a.u-tokyo.ac.jp/services/buddy/
Protein Data Bank
The authors thank Dr. John Mitchell and Dr. Michael Gilson for granting permission to use their datasets. The authors also thank Dr. Kazuya Sumikoshi for technical contributions. This work was partially supported by Grant-in-Aid for Young Scientists (B) and Grant-in-Aid for Scientific Research on Priority Areas Systems Genomics from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
- Najmanovich R, Kuttner J, Sobolev V, Edelman M: Side-Chain Flexibility in Proteins Upon Ligand Binding. Proteins. 2000, 39: 261-268. 10.1002/(SICI)1097-0134(20000515)39:3<261::AID-PROT90>3.0.CO;2-4.PubMedView ArticleGoogle Scholar
- Carlson HA: Protein flexibility and drug design: how to hit a moving target. Curr Opin Chem Biol. 2002, 6: 447-452. 10.1016/S1367-5931(02)00341-1.PubMedView ArticleGoogle Scholar
- Gutteridge A, Thornton J: Conformational Changes Observed in Enzyme Crystal Structures upon Substrate Binding. J Mol Biol. 2005, 346: 21-28. 10.1016/j.jmb.2004.11.013.PubMedView ArticleGoogle Scholar
- Gunasekaran K, Nussinov R: How Different are Structurally Flexible and Rigid Binding Sites? Sequence and Structural Features Discriminating Proteins that Do and Do not Undergo Conformational Change upon Ligand Binding. J Mol Biol. 2007, 365: 257-273. 10.1016/j.jmb.2006.09.062.PubMedView ArticleGoogle Scholar
- Brady GP, Stouten PFW: Fast prediction and visualization of protein binding pockets with PASS. J Computer-Aided Mol Design. 2000, 14: 383-401. 10.1023/A:1008124202956.View ArticleGoogle Scholar
- Laurie ATR, Jackson RM: Q-SiteFinder: an energy-based method for the prediction of protein-ligand binding sites. Bioinformatics. 2005, 21: 1908-1916. 10.1093/bioinformatics/bti315.PubMedView ArticleGoogle Scholar
- Morita M, Nakamura S, Shimizu K: Highly accurate method for ligand-binding site prediction in unbound state (apo) protein structures. Proteins. 2008, 73: 468-479. 10.1002/prot.22067.PubMedView ArticleGoogle Scholar
- Nissink JWM, Murray C, Hartshorn M, Verdonk ML, Cole JC, Taylor R: A New Test Set for Validating Predictions of Protein-Ligand Interaction. Proteins. 2002, 49: 457-471. 10.1002/prot.10232.PubMedView ArticleGoogle Scholar
- Meiler J, Baker D: ROSETTALIGAND: Protein-Small Molecule Docking with Full Side-Chain Flexibility. Proteins. 2006, 65: 538-548. 10.1002/prot.21086.PubMedView ArticleGoogle Scholar
- Hartshorn MJ, Verdonk ML, Chessari G, Brewerton SC, Mooij WTM, Mortenson PN, Murray CW: Diverse, High-Quality Test Set for the Validation of Protein-Ligand Docking Performance. J Med Chem. 2007, 50: 726-741. 10.1021/jm061277y.PubMedView ArticleGoogle Scholar
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000, 28: 235-242. 10.1093/nar/28.1.235.PubMedPubMed CentralView ArticleGoogle Scholar
- Shin JM, Cho DH: PDB-Ligand: a ligand database based on PDB for the automated and customized classification of ligand-binding structures. Nucleic Acids Res. 2005, 33: D238-D241.PubMedPubMed CentralView ArticleGoogle Scholar
- Dessailly BH, Lensink MF, Orengo CA, Wodak SJ: LigASite--a database of biologically relevant binding sites in proteins with known apo-structures. Nucleic Acids Res. 2008, 36: D667-D673.PubMedPubMed CentralView ArticleGoogle Scholar
- Ke HM, Zhang YP, Lipscomb WN: Crystal structure of fructose-1,6-bisphosphatase complexed with fructose 6-phosphate, AMP, and magnesium. Proc Natl Acad Sci USA. 1990, 87: 5243-5247. 10.1073/pnas.87.14.5243.PubMedPubMed CentralView ArticleGoogle Scholar
- Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007, 35: D198-D201. 10.1093/nar/gkl999.PubMedPubMed CentralView ArticleGoogle Scholar
- Puvanendrampillai D, Mitchell JBO: Protein Ligand Database (PLD): additional understanding of the nature and specificity of protein-ligand complexes. Bioinformatics. 2003, 19: 1856-1857. 10.1093/bioinformatics/btg243.PubMedView ArticleGoogle Scholar
- Block P, Sotriffer CA, Dramburg I, Klebe G: AffinDB: a freely accessible database of affinities for protein-ligand complexes from the PDB. Nucleic Acids Res. 2006, 34: D522-D526. 10.1093/nar/gkj039.PubMedPubMed CentralView ArticleGoogle Scholar
- Wang R, Fang X, Lu Y, Wang S: The PDBbind Database: Collection of Binding Affinities for Protein-Ligand Complexes with Known Three-Dimensional Structures. J Med Chem. 2004, 47: 2977-2980. 10.1021/jm030580l.PubMedView ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.