ACTIVITY: a database on DNA/RNA sites activity adapted to apply sequence-activity relationships from one system to another.

ACTIVITY is a database on DNA/RNA site sequences with known activity magnitudes, measurement systems, sequence-activity relationships under fixed experimental conditions and procedures to adapt these relationships from one measurement system to another. This database deposits information on DNA/RNA affinities to proteins and cell nuclear extracts, cutting efficiencies, gene transcription activity, mRNA translation efficiencies, mutability and other biological activities of natural sites occurring within promoters, mRNA leaders, and other regulatory regions in pro- and eukaryotic genomes, their mutant forms and synthetic analogues. Since activity magnitudes are heavily system-dependent, the current version of ACTIVITY is supplemented by three novel sub-databases: (i) SYSTEM, measurement systems; (ii) KNOWLEDGE, sequence-activity relationships under fixed experimental conditions; and (iii) CROSS_TEST, procedures adapting a relationship from one measurement system to another. These databases are useful in molecular biology, pharmacogenetics, metabolic engineering, drug design and biotechnology. The databases can be queried using SRS and are available through the Web, http://wwwmgs. bionet.nsc.ru/systems/Activity/.

rSNP_Guide, a database system for analysis of transcription factor binding to target sequences: application to SNPs and site-directed mutations.

rSNP_Guide is a novel curated database system for analysis of transcription factor (TF) binding to target sequences in regulatory gene regions altered by mutations. It accumulates experimental data on naturally occurring site variants in regulatory gene regions and site-directed mutations. This database system also contains the web tools for SNP analysis, i.e., active applet applying weight matrices to predict the regulatory site candidates altered by a mutation. The current version of the rSNP_Guide is supplemented by six sub-databases: (i) rSNP_DB, on DNA-protein interaction caused by mutation; (ii) SYSTEM, on experimental systems; (iii) rSNP_BIB, on citations to original publications; (iv) SAMPLES, on experimentally identified sequences of known regulatory sites; (v) MATRIX, on weight matrices of known TF sites; (vi) rSNP_Report, on characteristic examples of successful rSNP_Tools implementation. These databases are useful for the analysis of natural SNPs and site-directed mutations. The databases are available through the Web, http://wwwmgs.bionet.nsc.ru/mgs/systems/rsnp/.

Search for DNA conformational features for functional sites. Investigation of the TATA box.

A method for search of DNA conformational features significant for functional sites is developed. The method uses helical angles averaged for known X-ray structures. Nucleotide sequences are assigned mean angles in a given region. Choice of the significant angles is based on their capabilities to discriminate functional sites from random sequences. The yeast, invertebrate and vertebrate TATA boxes are analyzed using this method. Regions neighboring the TATA boxes are found to have smaller helical twist and roll angles. The results agree with the experimental data on Dickerson-Drew dodecamers. There is a significant decrease in the length of a small roll angle region with increasing complexity of taxon organization.

Nucleosomal DNA property database.

MOTIVATION: Chromatin structure plays the crucial role in proper gene functioning. Therefore, it is very important to investigate nucleosomal DNA properties and recognize genome nucleosome positioning sequences. Nevertheless, applying different sequence analysis methods separately is insufficient for complete nucleosomal DNA description. One of the most probable reasons for that is the weakness of nucleosome positioning signals. The present paper offers a set of methods to reveal the most important nucleosomal DNA characteristics and to show a common pattern of nucleosome site properties. RESULTS: A complex approach was used to determine conformational and physicochemical properties that are most significant for nucleosome binding site description. The integrated database of nucleosomal DNA properties is compiled. This database comprises different sections for description of DNA characteristics. Revealing significant DNA characteristics allows the classification of various samples of site sequences and the generation of programs for site recognition. AVAILABILITY: The current version of the database is available at http://wwwmgs.bionet.nsc. ru/system/BDNAvideo/. C-code of the recognition program may be found in the section FEATURE. WWW-available programs for testing arbitrary sequences are accessible at http://wwwmgs.bionet.nsc. ru/Programs/bDNA/NA_bDNA.htm/. The links to the mirror site(s) can be found at http://wwwmgs.bionet.nsc.ru/mgs/links/mirrors.html+ ++.

Conformational and physicochemical DNA features specific for transcription factor binding sites.

MOTIVATION: A reliable recognition of transcription factor binding sites is essential for analysis of regulatory genomic sequences. The experimental data make evident an important role of DNA conformational features for site functioning. However, Internet-available tools for revealing conformational and physicochemical DNA features significant for the site functioning and subsequent use of these features for site recognition have not been developed up to now. RESULTS: We suggest an approach for revealing significant conformational and physicochemical properties of functional sites implemented in the database B-DNA-VIDEO. This database is designed to study the sets of various transcription factor binding sites, providing evidence that transcription factor binding sites are characterized by specific sets of significant conformational and physicochemical DNA properties. For a fixed site, by using the B-DNA features selected for this site recognition, the C-program recognizing this site may be generated, control tested and stored in the database B-DNA-VIDEO. Each B-DNA-VIDEO entry links to the Web-applet recognizing the site, whose significant B-DNA features are stored in this entry as the 'site recognition programs'. The pairwise linked entry-applet pairs are compiled within the B-DNA-VIDEO system, which is simultaneously the database and the program tools package applicable immediately for recognizing the sites stored in the database. Indeed, this is the novelty. Hence, B-DNA-VIDEO is the Web resource of both 'searching for static data' and 'active computation' type, that is why it was called an 'activated database'. AVAILABILITY: B-DNA-VIDEO is available at http://wwwmgs.bionet.nsc.ru/systems/BDNAVideo/ and the mirror site at http://www.cbil.upenn.edu/mgs/systems/c onsfreq/.

SELEX_DB: an activated database on selected randomized DNA/RNA sequences addressed to genomic sequence annotation.

SELEX_DB is a novel curated database on selected randomized DNA/RNA sequences designed for accumulation of experimental data on functional site sequences obtained by using SELEX and SELEX-like technologies from the pools of random sequences. This database also contains the programs for DNA/RNA functional site recognition within arbitrary nucleotide sequences. The first release of SELEX_DB has been installed under SRS and is available through the WWW at http://wwwmgs.bionet.nsc.ru/mgs/systems/selex/

Oligonucleotide frequency matrices addressed to recognizing functional DNA sites.

MOTIVATION: Recognition of functional sites remains a key event in the course of genomic DNA annotation. It is well known that a number of sites have their own specific oligonucleotide content. This pinpoints the fact that the preference of the site-specific nucleotide combinations at adjacent positions within an analyzed functional site could be informative for this site recognition. Hence, Web-available resources describing the site-specific oligonucleotide content of the functional DNA sites and applying the above approach for site recognition are needed. However, they have been poorly developed up to now. RESULTS: To describe the specific oligonucleotide content of the functional DNA sites, we introduce the oligonucleotide alphabets, out of which the frequency matrix for a given site could be constructed in addition to a traditional nucleotide frequency matrix. Thus, site recognition accuracy increases. This approach was implemented in the activated MATRIX database accumulating oligonucleotide frequency matrices of the functional DNA sites. We have demonstrated that the false-positive error of the functional site recognition decreases if the oligonucleotide frequency matrixes are added to the nucleotide frequency matrixes commonly used. AVAILABILITY: The MATRIX database is available on the Web, http://wwwmgs.bionet.nsc.ru/Dbases/MATRIX/ and the mirror site, http://www.cbil.upenn.edu/mgs/systems/c onsfreq/.

Identification of sequence-dependent DNA features correlating to activity of DNA sites interacting with proteins.

MOTIVATION: The commonly accepted statistical mechanical theory is now multiply confirmed by using the weight matrix methods successfully recognizing DNA sites binding regulatory proteins in prokaryotes. Nevertheless, the recent evaluation of weight matrix methods application for transcription factor binding site recognition in eukaryotes has unexpectedly revealed that the matrix scores correlate better to each other than to the activity of DNA sites interacting with proteins. This observation points out that molecular mechanisms of DNA/protein recognition are more complicated in eukaryotes than in prokaryotes. As the extra events in eukaryotes, the following processes may be considered: (i) competition between the proteins and nucleosome core particle for DNA sites binding these proteins and (ii) interaction between two synergetic/antagonist proteins recognizing a composed element compiled from two DNA sites binding these proteins. That is why identification of the sequence-dependent DNA features correlating with affinity magnitudes of DNA sites interacting with a protein can pinpoint the molecular event limiting this protein/DNA recognition machinery. RESULTS: An approach for predicting site activity based on its primary nucleotide sequence has been developed. The approach is realized in the computer system ACTIVITY, containing the databases on site activity and on conformational and physicochemical DNA/RNA parameters. By using the system ACTIVITY, an analysis of some sites was provided and the methods for predicting site activity were constructed. The methods developed are in good agreement with the experimental data. AVAILABILITY: The database ACTIVITY is available at http://wwwmgs.bionet.nsc.ru/systems/Activity/ and the mirror site, http://www.cbil.upenn.edu/mgs/systems/acti vity/.