Search

The PDBSite database provides comprehensive structural and functional information on various protein sites (post-translational modification, catalytic active, organic and inorganic ligand binding, protein–protein, protein–DNA and protein–RNA interactions) in the Protein Data Bank (PDB). The PDBSite is available online at http://wwwmgs.bionet.nsc.ru/mgs/gnw/pdbsite/. It consists of functional sites extracted from PDB using the SITE records and of an additional set containing the protein interaction sites inferred from the contact residues in heterocomplexes. The PDBSite was set up by automated processing of the PDB. The PDBSite database can be queried through the functional description and the structural characteristics of the site and its environment. The PDBSite is integrated with the PDBSiteScan tool allowing structural comparisons of a protein against the functional sites. The PDBSite enables the recognition of functional sites in protein tertiary structures, providing annotation of function through structure. The PDBSite is updated after each new PDB release.

PDBSiteScan is a web-accessible program designed for searching three-dimensional (3D) protein fragments similar in structure to known active, binding and posttranslational modification sites. A collection of known sites we designated as PDBSite was set up by automated processing of the PDB database using the data on site localization in the SITE field. Additionally, protein-protein interaction sites were generated by analysis of atom coordinates in heterocomplexes. The total number of collected sites was more than 8100; they were assigned to more than 80 functional groups. PDBSiteScan provides automated search of the 3D protein fragments whose maximum distance mismatch (MDM) between N, Calpha and C atoms in a fragment and a functional site is not larger than the MDM threshold defined by the user. PDBSiteScan requires perfect matching of amino acids. PDBSiteScan enables recognition of functional sites in tertiary structures of proteins and allows proteins with functional information to be annotated. The program PDBSiteScan is available at http://wwwmgs.bionet.nsc.ru/mgs/systems/fastprot/pdbsitescan.html.

The recognition of the structural/functional determinants in proteins has broad implications for structural and functional genomics. A better understanding of these determinants, such as protein-protein, protein-DNA, and protein-RNA interaction sites, would provide insight into protein functions. A computational workbench for the recognition of functional sites in protein tertiary structure combined with molecular complex reconstruction, estimation of mutation effect on protein thermodynamic stability, as well as search for the structure-activity relationships in homologous protein set was developed. Here, we illustrate the capabilities of the workbench by providing examples of (1) search for interactions of the hepatitis C virus proteins with the human proteins, (2) analysis of the potential toxicity of molecular compounds, (3) analysis of structure-activity relationships in the disintegrin family, and (4) structural protein classification based on the structural similarity to the functional sites.

The goal of creation of the Transcription Regulatory Regions Database (TRRD) was to provide a complete and adequate description of the structure-function organization of transcription regulatory regions in eukaryotic genes. TRRD contains only experimentally confirmed data about (i) transcription factor binding sites; (ii) regulatory units (promoter regions, enhancers, and silencers); and (iii) locus control regions. The main tool for searching TRRD and navigation in it is SRS. TRRD has hierarchically organized vocabularies and thesauruses used for developing specialized data retrieval tools. The current TRRD release contains information about 2308 eukaryotic genes (of them, 34 % are human genes) inputted basing on annotation of 7565 scientific papers. For these genes, the largest in the world sets of experimentally confirmed regulatory units (3439) and transcription factor binding sites (10 045) are collected in TRRD. Of them, 37 % of regulatory units and 38 % of binding sites are related to human genes. This paper characterizes groups of experiments basing on which regulatory units and binding sites are annotated. Examples of TRRD entries are given. The database is available at http://www.bionet.nsc.ru/trrd/.

The local DNA conformation in the region of transcription factor binding sites, determined by context, is one of the factors underlying the specificity of DNA-protein interactions. Analysis of the local conformation of a set of functional DNA sequences may allow for determination of the conservative conformational and physicochemical parameters reflecting molecular mechanisms of interaction. The web resource SITECON is designed to detect conservative conformational and physicochemical properties in transcription factor binding sites, contains a knowledge base of conservative properties for >100 high-quality sample sites and allows for recognition of potential transcription factor binding sites based on conservative properties from both the knowledge base and the results of analysis of a sample proposed by a user. The resource SITECON is available at http://wwwmgs.bionet.nsc.ru/mgs/programs/sitecon/.

An Internet-oriented program PDBSiteScan making structural alignment of the sites contained in the database PDBSite with 3D structure of a user-specified protein was developed. The program automatically selects all the variants where the maximal distances with respect to N, Cα and C atoms of the fragment’s residues in 3D structures of the protein studied and the site do not exceed a user-specified value. An indispensable condition in this realization of the method was identity of the types of amino acids for superposed residue pairs. PDBSiteScan may be used for recognition of functional sites in protein 3D structures and is available at http://wwwmgs.bionet.nsc.ru/mgs/ systems/fastprot/pdbsitescan.html.

We have developed PROF_PAT, a database of patterns, constructed for groups of related proteins and designed to maximize representation of amino acid sequences from the SWISS-PROT database. The purpose of the current study was to demonstrate that PROT_PAT is not only as good as known analogs but surpasses them in some features. 10938 new amino acid sequences from the SWISS-PROT bank were compared with patterns constructed for protein families in the PROF_PAT 1.10 bank. The aim of the comparisons was to estimate some threshold values of "Score" parameter to distinguish random similarities from significant ones. From the 10938 new sequences, 638 did not reveal any similarities with PROF_PAT patterns. Cases of found similarities were divided into three sets: 'positive', 'putative' (or 'unknown'), and 'false positive', containing 7719, 2297 and 284 sequences respectively. Using 20 amino acid sequences from the TrEMBL bank that have no descriptions, PROF_PAT demonstrated specificity at a level that was as good as the best-known "secondary" banks. At the same time, its pattern content and variety of included proteins was significantly richer, and its search speed was 3-10 times higher than those of any other protein family bank used for comparison.

We report an object-oriented data handler and supplementary tools for the development of molecular genetics application software for various sequence analyses. Our data handler has a flexible and expandable format that supports the most common data types for molecular genetic software. New data types can be constructed in an object-oriented manner from the basic units. The data handler includes an object library, a format-converting program and a viewer that can visualize simultaneously the data contained in several files to construct a general picture from separate data. This software has been implemented on an IBM PC-compatible personal computer.