Nucleic Acids Research 2006 34(Database Issue):D195-D198; doi:10.1093/nar/gkj017
Nucleic Acids Research, 2006, Vol. 34, Database issue D195-D198
© The Author 2006. Published by Oxford University Press. All rights reserved
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PINT: Protein–protein Interactions Thermodynamic Database
M. D. Shaji Kumar* and
M. Michael Gromiha1
Department of Biochemical Engineering and Science, Kyushu Institute of Technology Iizuka 820-8502, Fukuoka, Japan
1Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST) AIST Tokyo Waterfront Bio-IT Research Building, 2-42 Aomi, Koto-ku, Tokyo 135-0064, Japan
*To whom correspondence should be addressed. Tel: +81 948 29 7831; Fax: +81 948 29 7841; Email: shaji{at}bse.kyutech.ac.jp
Received August 15, 2005. Revised September 17, 2005. Accepted September 17, 2005.
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ABSTRACT
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The first release of Protein–protein Interactions Thermodynamic
Database (PINT) contains >1500 data of several thermodynamic
parameters along with sequence and structural information, experimental
conditions and literature information. Each entry contains numerical
data for the free energy change, dissociation constant, association
constant, enthalpy change, heat capacity change and so on of
the interacting proteins upon binding, which are important for
understanding the mechanism of protein–protein interactions.
PINT also includes the name and source of the proteins involved
in binding, their Protein Information Resource, SWISS-PROT and
Protein Data Bank (PDB) codes, secondary structure and solvent
accessibility of residues at mutant positions, measuring methods,
experimental conditions, such as buffers, ions and additives,
and literature information. A WWW interface facilitates users
to search data based on various conditions, feasibility to select
the terms for output and different sorting options. Further,
PINT is cross-linked with other related databases, PIR, SWISS-PROT,
PDB and NCBI PUBMED literature database. The database is freely
available at
http://www.bioinfodatabase.com/pint/index.html
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INTRODUCTION
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Protein–protein interactions play a key role in many biological
processes such as signal transduction, gene expression and control,
antibody–antigen complex and so on. Deciphering the details
of interactions between the residues at protein–protein
interface and the identification of binding sites are challenging
problems in Computational Biology/Bioinformatics (
1–
3).
The integration of structural data and thermodynamic parameters
of protein–protein complexes would improve our knowledge
and pave a way to understand their binding specificity and functions.
Although the structural data of protein–protein complexes
have been accumulated in Protein Data Bank (PDB) (
4) the thermodynamic
data, such as binding free energy change, association/dissociation
constant, heat capacity change and so on are not yet well documented.
We have developed a database, Protein–protein Interactions
Thermodynamic Database, PINT, which contains experimental data
of several thermodynamic parameters along with sequence and
structural information, measuring methods, experimental conditions
and literature information. This database has potential applications
for understanding the relationship between binding specificity
and the factors that are influencing protein–protein interactions.
We have developed a WWW interface to facilitate searching the
database and sorting outputs.
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CONTENTS OF THE DATABASE
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Each entry in the database is identified by a PINT database
code and includes the following information.
Protein and peptide details. Protein/peptide name, source, domain, respective PIR (5), SWISS-PROT (6) and PDB (4) codes, information about wild-type and nature of mutations (single, double and multiple), secondary structure and solvent accessibility of residues at mutant positions. The solvent accessible surface area of all the residues was calculated and the secondary structure assignments of each mutant were made using the program DSSP (7). We have also provided the PDB code for the protein–protein complex. In PINT, the protein/peptide assignment was made based on the experiments, and not according to the size of the interacting protein/peptide. For example, for isothermal titration calorimetry (ITC) experiments, we have assigned the reactant inside the reaction cell as protein and the reactant getting injected as peptide.
Experimental conditions. Temperature, pH, protein and peptide concentrations, buffer, ion, additives and measuring method.
Thermodynamic data. Dissociation constant (Kd), association constant (Ka), free energy change (
G), enthalpy change (H) and heat capacity change (Cp) of the interacting proteins upon binding. The changes in Kd, Ka and G have also been provided for mutants as Kd, Ka and G, respectively.
Literature information. Keywords, authors, reference and PMID.
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DATABASE STATISTICS
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The first release of PINT, version 1.0, contains 1513 entries
from 72 original research articles. PINT has 129 protein–protein
complexes and 33 of them have complete 3D structures, which
are deposited in PDB. Majority of the data were obtained with
ITC experiments (670) followed by surface plasmon resonance
(SPR) (322) and Fluorescence (216).
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ACCESS TO PINT
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PINT can be accessed through World Wide Web at
http://www.bioinfodatabase.com/pint/index.html.
We have implemented both quick and advanced search options in
PINT database. In the advanced search, various options are available
in the interface, as shown in
Figure 1, and are briefly explained
below. (i) Retrieving data for a particular protein/peptide.
For the convenience to the users, we have provided the complete
list in a pull down menu. (ii) Specifying the codes, PIR (
5),
SWISS-PROT (
6) and PDB (
4). (iii) Searching the data based on
secondary structure and solvent accessibility of protein/peptide
mutants. (iv) Extracting the data for a particular measurement
(ITC, Fluorescence, Electrophysiology, Spectrophotometry, SPR
and so on). (v) Obtaining the data for specific range of T,
pH,
Kd,
Ka,
G,
H and
Cp. (vi) Limiting the data to specific
years or journals. (vii) Searching with keywords, journal, PMID
and authors' names.
Detailed tutorials describing the usage of the present PINT
are available at the home page. As an example, the necessary
items to be filled/selected to search the thermodynamic data,
dissociation constant and free energy change for protein–protein
complexes obtained in the temperature range of 15–30°
and pH >5 are shown in
Figure 1a. In the same figure, we
have shown the display items in the output by tick marks. In
PINT, it is possible to sort the data by T, pH,
Kd,
G and so
on and we showed the sorting with
G in descending order. This
search picked up 1174 data and a part of the results obtained
with the search conditions and sorting option is shown in
Figure 1b.
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GUIDELINES
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We have provided a detailed help page explaining about the contents
of the database and different modes of search options. Further,
we have given the lists of PINT codes, protein and peptide names,
buffers, ions and additives, PIR, SWISS-PROT and PDB codes and
authors. This will assist the users to obtain the relevant data
quickly.
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COMPARISON WITH OTHER RELATED DATABASES
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Salwinski
et al. (
8) developed a Database of Interacting Proteins,
which mainly contains the information about the relationship
between protein structure and function and the thermodynamic
data are minimal. The Biomolecular Interaction Network Database,
archives biomolecular interaction, reaction, complex and pathway
information (
9). The Kinetic Data of Bio-molecular Interactions,
aimed at providing experimentally determined kinetic data of
protein–protein and other complexes (
10). In the present
work, we have developed a database, PINT, which mainly accumulates
the thermodynamic data of interacting proteins upon binding.
We have provided all the experimentally measured thermodynamic
data (
Kd,
Ka,
G,
H and
Cp) for wild-type and mutant proteins.
PINT differs from all other existing databases and it will be
useful to understand the relationship among sequence, structure
and binding specificities of protein–protein complexes.
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LINKS TO OTHER DATABASES
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Each data in PINT is linked to the sequence databases PIR (
5)
and SWISS-PROT (
6), structure database, PDB (
4), and the literature
database, PUBMED (
http://www.ncbi.nlm.nih.gov/entrez/). Further,
general links are given to related protein–protein interaction
and other databases (
8–
10).
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AVAILABILITY AND CITATION OF PINT
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The database is freely available for academic purpose at
http://www.bioinfodatabase.com/pint/index.html.
The users of PINT should cite this article, including the URL.
Suggestions and other materials for inclusion in the database
are welcome and should be sent to
admin{at}bioinfodatabase.com.
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ACKNOWLEDGEMENTS
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Funding to pay the Open Access publication charges for this
article were waived by Oxford University Press.
Conflict of interest statement. None declared.
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REFERENCES
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