[Molecular Mechanisms to Optimize Gene Translation Elongation Differ Significantly in Bacteria with and without Nonribosomal Peptides].

Nonribosomal peptides play an important role in the vital activity of bacteria and have an extremely broad field of biological activity. In particular, they act as antibiotics, toxins, surfactants, siderophores, and also perform a number of other specific functions. Biosynthesis of these molecules does not occur on ribosomes but by special enzymes that form gene clusters in bacterial genomes. We hypothesized that the presence of nonribosomal peptide synthesis pathways is a specific feature of bacterial metabolism, which may affect other vital processes of the cell, including translational ones. This work was the first to show the relationship between the translation regulation mechanism of protein-coding genes in bacteria, which is largely determined by the efficiency of translation elongation, and the presence of gene clusters in the genomes for the biosynthesis of nonribosomal peptides. Bioinformatic analysis of the translation elongation efficiency of protein-coding genes was performed in 11679 bacterial genomes, some of which contained gene clusters of nonribosomal peptide biosynthesis and some of which did not. The analysis showed that bacteria whose genomes contained clusters of nonribosomal peptide biosynthetic genes and those without such gene clusters differ significantly in the molecular mechanisms that ensure translation efficiency. Thus, among microorganisms whose genomes contain gene clusters of nonribosomal peptide synthetases, a significantly smaller part of them is characterized by optimized regulation of the number of local inverted repeats, while most of them have genomes optimized by the averaged energy of inverted repeats studs in mRNA and additionally by codon composition. Our results suggest that the presence of nonribosomal peptide biosynthetic pathways in bacteria may influence the structure of the overall bacterial metabolism, which is also expressed in the specific mechanisms of ribosomal protein biosynthesis.

[Hypothetical SNP Markers That Significantly Affect the Affinity of the TATA-Binding Protein to VEGFA, ERBB2, IGF1R, FLT1, KDR, and MET Oncogene Promoters as Chemotherapy Targets].

The following hypothesis has been proposed: IF an SNP can significantly increase the expression of an oncogene by increasing the affinity of the TATA-binding protein (TBP) to its promoter, THEN this SNP can also reduce the apparent bioactivity of inhibitors of this oncogene during antitumor chemotherapy and vice versa. In the context of this hypothesis, the previously proposed method (http://beehive.bionet.nsc. ru/cgi-bin/mgs/tatascan/start.pl) was applied to analyze all SNPs found within the [-70; -20] regions (which harbor all proven TBP-binding sites) of the promoters of VEGFA, EGFR, ERBB2, IGF1R, FLT1, KDR, and MET oncogenes according to the human reference genome, hg19. For 83% of these SNPs, their effect on TBP affinity to the oncogene promoters required for assembly of preinitiation complexes was not significant. rs36208385, rs36208384, rs370995111, rs372731987, rs111811434, rs369547510, rs76407893, rs369728300, and rs72001900 can potentially serve as SNP markers to reduce the apparent bioactivity of oncogene inhibitors, while rs141092704, rs184083669, rs145139616, rs200697953, rs187746433, rs199730913, rs377370642, rs114484350, rs374921120, rs146790957, rs376727645, and rs72001900 can be the markers for enhancing this activity.

[Regulatory Genomics: Integrated Experimental and Computer Approaches].

The review describes integrated experimental and computer approaches to the investigation of the mechanisms of transcriptional regulation of the organization of eukaryotic genes and transcription regulatory regions. These include (a) an analysis of the factors affecting the affinity of TBP (TATA-binding protein) for the TATA box; (b) research on the patterns of chromatin mark distributions and their role in the regulation of gene expression; (c) a study of 3D chromatin organization; (d) an estimation of the effects of polymorphisms on gene expression via high-resolution Chip-seq and DNase-seq techniques. It was demonstrated that integrated experimental and computer approaches are very important for the current understanding of transcription regulatory mechanisms and the structural and functional organization of the regulatory regions controlling transcription.

Nasal aerodynamics protects brain and lung from inhaled dust in subterranean diggers, Ellobius talpinus.

Inhalation of air-dispersed sub-micrometre and nano-sized particles presents a risk factor for animal and human health. Here, we show that nasal aerodynamics plays a pivotal role in the protection of the subterranean mole vole Ellobius talpinus from an increased exposure to nano-aerosols. Quantitative simulation of particle flow has shown that their deposition on the total surface of the nasal cavity is higher in the mole vole than in a terrestrial rodent Mus musculus (mouse), but lower on the olfactory epithelium. In agreement with simulation results, we found a reduced accumulation of manganese in olfactory bulbs of mole voles in comparison with mice after the inhalation of nano-sized MnCl2 aerosols. We ruled out the possibility that this reduction is owing to a lower transportation from epithelium to brain in the mole vole as intranasal instillations of MnCl2 solution and hydrated nanoparticles of manganese oxide MnO · (H2O)x revealed similar uptake rates for both species. Together, we conclude that nasal geometry contributes to the protection of brain and lung from accumulation of air-dispersed particles in mole voles.

[Aerosol deposition in nasal passages of burrowing and ground rodents when breathing dust-laden air].

In subterranean rodents, which dig down the passages with frontal teeth, adaptation to the underground mode of life presumes forming of mechanisms that provide protection against inhaling dust particles of different size when digging. One of such mechanisms can be specific pattern of air flow organization in the nasal cavity. To test this assumption, comparative study of geometry and aerodynamics of nasal passages has been conducted with regard to typical representative of subterranean rodents, the mole vole, and a representative of ground rodents, the house mouse. Numerical modeling of air flows and deposition of micro- and nanoparticle aerosols indicates that sedimentation of model particles over the whole surface of nasal cavity is higher in mole vole than in house mouse. On the contrary, particles deposition on the surface of olfactory epithelium turns out to be substantially less in the burrowing rodent as compared to the ground one. Adaptive significance of the latter observation has been substantiated by experimental study on the uptake ofnanoparticles of hydrated manganese oxide MnO x (H2O)x and Mn ions from nasal cavity into brain. It has been shown with use of magnetic resonance tomography method that there is no difference between studied species with respect to intake of particles or ions by olfactory bulb when they are introduced intranasally. Meanwhile, when inhaling nanoparticle aerosol of MnCl2, deposition of Mn in mouse's olfactory bulbs surpasses markedly that in vole's bulbs. Thereby, the morphology of nasal passages as a factor determining the aerodynamics of upper respiratory tract ensures for burrowing rodents more efficient protection of both lungs and brain against inhaled aerosols than for ground ones.

[Permanent proteins in healthy human's urine in the experiment with 520-day isolation].

Purpose of the study was to track permanent proteins of urine proteome in the 520-day isolation experiment at the IBMP Ground-Based Test Facility with controlled environmental parameters. Object of the investigation was urine sampled from 6 normal male subjects at the age of 25 to 37 years. Second morning aliquots were gathered during baseline data collection, on days 50, 93, 124, 153, 180, 251, 274, 303, 330, 371, 400 and 427 of isolation, and in 7 days after its completion. Samples were subject to chromatography-mass spectrometry; results were analyzed with the help of bioinformatics resources. The following 7 permanent proteins were observed in urine over the entire length of the investigation: epidermal growth factor, polymer immunoglobulin receptor, plasma serine protease inhibitor, protein AMBP, keratin, type II cytoskeletal 1, collagen alpha-1 (vi) chain, serum albumin.

Stimulation of mouse hematopoietic stem cells by angiogenin and DNA preparations.

Immature hematopoietic progenitors are a constant source for renewal of hemocyte populations and the basic component of the tissue and cell repair apparatus. A unique property of these cells of internalizing extracellular double-stranded DNA has been previously shown. The leukostimulatory effect demonstrated in our pioneering studies was considered to be due to the feature of this cell. In the present research, we have analyzed the effects of DNA genome reconstructor preparation (DNAgr), DNAmix, and human recombinant angiogenin on both hematopoietic stem cells and multipotent progenitors. Treatment with bone marrow cells of experimental mice with these preparations stimulates colony formation by hematopoietic stem cells and proliferation of multipotent descendants. The main lineage responsible for this is the granulocyte-macrophage hematopoietic lineage. Using fluorescent microscopy as well as FACS assay, co-localization of primitive c-Kit- and Sca-1-positive progenitors and the TAMRA-labeled double-stranded DNA has been shown. Human recombinant angiogenin was used as a reference agent. Cells with specific markers were quantified in intact bone marrow and colonies grown in the presence of inducers. Quantitative analysis revealed that a total of 14,000 fragment copies of 500 bp, which is 0.2% of the haploid genome, can be delivered into early progenitors. Extracellular double-stranded DNA fragments stimulated the colony formation in early hematopoietic progenitors from the bone marrow, which assumed their effect on cells in G0. The observed number of Sca1+/c-Kit+ cells in colonies testifies to the possibility of both symmetrical and asymmetrical division of the initial hematopoietic stem cell and its progeny.

[Regulatory transcription codes in eukaryotic genomes].

Key aspects of gene transcription regulation in multicellular organisms, including the characteristics of their promoters, transcription-factor binding sites, and composition elements are reviewed. The functional role of transcription regulatory proteins (basal factors and regulatory transcription factors), and the mechanisms responsible for regulation of their activity are also discussed. Furthermore, we describe the importance of DNA-encoded nucleosome organization and chromatin modifications in the course of transcription regulation, as well as some mechanisms that regulate the activity of transcription factors associated with genetic networks. The current outlook on regulatory gene expression codes in eukaryotes is presented.

[Replication of the subgenomic hepatitis C virus replicon in the presence of the NS3 protease inhibitors: a stochastic model].

The hepatitis C virus (HCV) belongs to Flaviviridae family and causes hazardous liver diseases leading frequently to cirrhosis and hepatocellular carcinoma. HCV is able to rapidly acquire drug resistance and for this reason there is currently no effective anti-HCV therapy in spite of appearance of new potential drugs. Mathematical models are relevant to predict the efficacy of potential drugs against virus or host targets. One of the promising targets for development of new drugs is the viral NS3 protease. Here we developed a stochastic model of the subgenomic HCV replicon replication in Huh-7 cells and in the presence of the NS3 protease inhibitors. Along with consideration of the stochastic nature of the subgenomic HCV replicon replication the model takes into account the existence and generation of main NS3 protease drug resistant mutants, namely BILN-2061 (A156T, D168V, R155Q), VX-950 (A156S, A156T, T54A) and SCH-503034 (A156T, A156S, T54A). The model reproduces well the viral RNA kinetics in the cell from the moment of the subgenomic HCV replicon transfection to steady state, as well as the viral RNA suppression kinetics in the presence of NS3 protease inhibitors BILN-2061, VX-950 and SCH-503034. We showed that the resistant mutants should be taken into account for the correct description of biphasic kinetics of the viral RNA suppression. The mutants selected in the presence of different inhibitor concentrations have maximal replication capacity in the given inhibitor concentration range. Our model can be used to interpret the results of the new anti-HCV drug testing in replicon systems, as well as to predict the efficacy of new potential drugs and optimize the regimen of their use.

On the Role of TATA Boxes and TATA-Binding Protein in Arabidopsis thaliana.

For transcription initiation by RNA polymerase II (Pol II), all eukaryotes require assembly of basal transcription machinery on the core promoter, a region located approximately in the locus spanning a transcription start site (-50; +50 bp). Although Pol II is a complex multi-subunit enzyme conserved among all eukaryotes, it cannot initiate transcription without the participation of many other proteins. Transcription initiation on TATA-containing promoters requires the assembly of the preinitiation complex; this process is triggered by an interaction of TATA-binding protein (TBP, a component of the general transcription factor TFIID (transcription factor II D)) with a TATA box. The interaction of TBP with various TATA boxes in plants, in particular Arabidopsis thaliana, has hardly been investigated, except for a few early studies that addressed the role of a TATA box and substitutions in it in plant transcription systems. This is despite the fact that the interaction of TBP with TATA boxes and their variants can be used to regulate transcription. In this review, we examine the roles of some general transcription factors in the assembly of the basal transcription complex, as well as functions of TATA boxes of the model plant A. thaliana. We review examples showing not only the involvement of TATA boxes in the initiation of transcription machinery assembly but also their indirect participation in plant adaptation to environmental conditions in responses to light and other phenomena. Examples of an influence of the expression levels of A. thaliana TBP1 and TBP2 on morphological traits of the plants are also examined. We summarize available functional data on these two early players that trigger the assembly of transcription machinery. This information will deepen the understanding of the mechanisms underlying transcription by Pol II in plants and will help to utilize the functions of the interaction of TBP with TATA boxes in practice.

Evolution of human genes encoding cell surface receptors involved in the regulation of appetite: an analysis based on the phylostratigraphic age and divergence indexes.

Genes encoding cell surface receptors make up a significant portion of the human genome (more than a thousand genes) and play an important role in gene networks. Cell surface receptors are transmembrane proteins that interact with molecules (ligands) located outside the cell. This interaction activates signal transduction pathways in the cell. A large number of exogenous ligands of various origins, including drugs, are known for cell surface receptors, which accounts for interest in them from biomedical researchers. Appetite (the desire of the animal organism to consume food) is one of the most primitive instincts that contribute to survival. However, when the supply of nutrients is stable, the mechanism of adaptation to adverse factors acquired in the course of evolution turned out to be excessive, and therefore obesity has become one of the most serious public health problems of the twenty-first century. Pathological human conditions characterized by appetite violations include both hyperphagia, which inevitably leads to obesity, and anorexia nervosa induced by psychosocial stimuli, as well as decreased appetite caused by neurodegeneration, inflammation or cancer. Understanding the evolutionary mechanisms of human diseases, especially those related to lifestyle changes that have occurred over the past 100-200 years, is of fundamental and applied importance. It is also very important to identify relationships between the evolutionary characteristics of genes in gene networks and the resistance of these networks to changes caused by mutations. The aim of the current study is to identify the distinctive features of human genes encoding cell surface receptors involved in appetite regulation using the phylostratigraphic age index (PAI) and divergence index (DI). The values of PAI and DI were analyzed for 64 human genes encoding cell surface receptors, the orthologs of which were involved in the regulation of appetite in model animal species. It turned out that the set of genes under consideration contains an increased number of genes with the same phylostratigraphic age (PAI = 5, the stage of vertebrate divergence), and almost all of these genes (28 out of 31) belong to the superfamily of G-protein coupled receptors. Apparently, the synchronized evolution of such a large group of genes (31 genes out of 64) is associated with the development of the brain as a separate organ in the first vertebrates. When studying the distribution of genes from the same set by DI values, a significant enrichment with genes having a low DIs was revealed: eight genes (GPR26, NPY1R, GHSR, ADIPOR1, DRD1, NPY2R, GPR171, NPBWR1) had extremely low DIs (less than 0.05). Such low DI values indicate that most likely these genes are subjected to stabilizing selection. It was also found that the group of genes with low DIs was enriched with genes that had brain-specific patterns of expression. In particular, GPR26, which had the lowest DI, is in the group of brain-specific genes. Because the endogenous ligand for the GPR26 receptor has not yet been identified, this gene seems to be an extremely interesting object for further theoretical and experimental research. We believe that the features of the genes encoding cell surface receptors we have identified using the evolutionary metrics PAI and DI can be a starting point for further evolutionary analysis of the gene network regulating appetite.

Reconstruction and analysis of the gene regulatory network for cell wall function in Arabidopsis thaliana L. leaves in response to water deficit.

The plant cell wall represents the outer compartment of the plant cell, which provides a physical barrier and triggers signaling cascades under the influence of biotic and abiotic stressors. Drought is a factor that negatively affects both plant growth and development. Cell wall proteins (CWP) play an important role in the plant response to water deficit. The adaptation mechanisms of the cell wall to water loss are of interest for identifying important genetic factors determining plant drought resistance and provide valuable information on biomarkers for further selection aimed at increasing the yield of crop plants. Using ANDSystem, a gene network describing the regulation of CWPs under water restriction conditions was reconstructed. The analysis of the gene network and the transcriptome data analysis allowed prioritizing transcription factors (TF) based on their enrichment of differentially expressed genes regulated by them. As a result, scores were calculated, acting as indicators of the association of TFs with water deficit. On the basis of the score values, eight most significant TFs were selected. The highest priority was given to the TF GBF3. CWPs were prioritized according to the criterion of summing up the scores of transcription factors regulating these genes. Among the most prioritized CWPs were the AT5G03350 gene encoding a lectin-like protein, AT4G20860 encoding BBE-like 22 required for the oxidation of cellulose degradation products, and AT4G37800 encoding xyloglucan endotransglucosylase/ hydrolase 7. Overall, the implemented algorithm could be used for prediction of regulatory interactions between transcription factors and target genes encoding cell wall proteins in plants.

Gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative delirium.

Postoperative delirium (POD) is considered one of the most severe complications, resulting in impaired cognitive function, extended hospitalization, and higher treatment costs. The challenge of early POD diagnosis becomes particularly significant in cardiac surgery cases, as the incidence of this complication exceeds 50 % in certain patient categories. While it is known that neuroinflammation, neurotransmitter imbalances, disruptions in neuroendocrine regulation, and interneuronal connections contribute significantly to the development of POD, the molecular, genetic mechanisms of POD in cardiac surgery patients, along with potential metabolomic diagnostic markers, remain inadequately understood. In this study, blood plasma was collected from a group of patients over 65 years old after cardiac surgery involving artificial circulation. The collected samples were analyzed for sphingomyelin content and quantity using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS) methods. The analysis revealed four significantly different sphingomyelin contents in patients with POD compared to those who did not develop POD (control group). Employing gene network reconstruction, we perceived a set of 82 regulatory enzymes affiliated with the genetic coordination of the sphingolipid metabolism pathway. Within this set, 47 are assumed to be regulators of gene expression, governing the transcription of enzymes pivotal to the metabolic cascade. Complementing this, an additional assembly of 35 regulators are considered to be regulators of activity, degradation, and translocation dynamics of enzymes integral to the aforementioned pathway. Analysis of the overrepresentation of diseases with which these regulatory proteins are associated showed that the regulators can be categorized into two groups, associated with cardiovascular pathologies (CVP) and neuropsychiatric diseases (NPD), respectively. The regulators associated with CVP are expectedly related to the effects on myocardial tissue during surgery. It is hypothesized that dysfunction of NPD-associated regulators may specifically account for the development of POD after cardiac surgery. Thus, the identified regulatory genes may provide a basis for planning further experiments, in order to study disorders at the level of expression of these genes, as well as impaired function of proteins encoded by them in patients with POD. The identified significant sphingolipids can be considered as potential markers of POD.

Combined in silico/in vivo analysis of mechanisms providing for root apical meristem self-organization and maintenance.

BACKGROUND AND AIMS: The root apical meristem (RAM) is the plant stem cell niche which provides for the formation and continuous development of the root. Auxin is the main regulator of RAM functioning, and auxin maxima coincide with the sites of RAM initiation and maintenance. Auxin gradients are formed due to local auxin biosynthesis and polar auxin transport. The PIN family of auxin transporters plays a critical role in polar auxin transport, and two mechanisms of auxin maximum formation in the RAM based on PIN-mediated auxin transport have been proposed to date: the reverse fountain and the reflected flow mechanisms. METHODS: The two mechanisms are combined here in in silico studies of auxin distribution in intact roots and roots cut into two pieces in the proximal meristem region. In parallel, corresponding experiments were performed in vivo using DR5::GFP Arabidopsis plants. KEY RESULTS: The reverse fountain and the reflected flow mechanism naturally cooperate for RAM patterning and maintenance in intact root. Regeneration of the RAM in decapitated roots is provided by the reflected flow mechanism. In the excised root tips local auxin biosynthesis either alone or in cooperation with the reverse fountain enables RAM maintenance. CONCLUSIONS: The efficiency of a dual-mechanism model in guiding biological experiments on RAM regeneration and maintenance is demonstrated. The model also allows estimation of the concentrations of auxin and PINs in root cells during development and under various treatments. The dual-mechanism model proposed here can be a powerful tool for the study of several different aspects of auxin function in root.

[Reconstruction of associative protein networks connected with processes of sodium exchange' regulation and sodium deposition in healthy volunteers by urine proteome analysis].

The study was conducted during the experiment with 105-day isolation in experimental complex. In the present investigation we collected urine samples from 6 healthy volunteers. The physical activity, diurnal rhythm, temperature parameters and level of oxygen and carbon dioxide were controlled during the experiment. According to the program, food intake (electrolytes, water, calories, fat, carbohydrates, protein, vitamins, etc.) on each stage of experiment was normalized. All samples were analyzed using mass spectrometer of an ionic cyclotron resonance with transformation of Fure LTQ FT MS (Thermo) on the basis of the AMT-tags (accurate mass and time tags) approach. Among more than 20 000 we found out 690 proteotypical proteins and we identified about 600 urine proteins. For physiological interpretation of the proteome data we used computer systems ANDCell and ANDVisio. Clustering of proteins and application of these systems revealed proteins that are most closely associated with the regime of sodium intake, as well as build the network of their interactions.

Rational metabolic engineering of Corynebacterium glutamicum to create a producer of L-valine.

L-Valine is one of the nine amino acids that cannot be synthesized de novo by higher organisms and must come from food. This amino acid not only serves as a building block for proteins, but also regulates protein and energy metabolism and participates in neurotransmission. L-Valine is used in the food and pharmaceutical industries, medicine and cosmetics, but primarily as an animal feed additive. Adding L-valine to feed, alone or mixed with other essential amino acids, allows for feeds with lower crude protein content, increases the quality and quantity of pig meat and broiler chicken meat, as well as improves reproductive functions of farm animals. Despite the fact that the market for L-valine is constantly growing, this amino acid is not yet produced in our country. In modern conditions, the creation of strains-producers and organization of L-valine production are especially relevant for Russia. One of the basic microorganisms most commonly used for the creation of amino acid producers, along with Escherichia coli, is the soil bacterium Corynebacterium glutamicum. This review is devoted to the analysis of the main strategies for the development of L- valine producers based on C. glutamicum. Various aspects of L-valine biosynthesis in C. glutamicum are reviewed: process biochemistry, stoichiometry and regulation, enzymes and their corresponding genes, export and import systems, and the relationship of L-valine biosynthesis with central cell metabolism. Key genetic elements for the creation of C. glutamicum-based strains-producers are identified. The use of metabolic engineering to enhance L-valine biosynthesis reactions and to reduce the formation of byproducts is described. The prospects for improving strains in terms of their productivity and technological characteristics are shown. The information presented in the review can be used in the production of producers of other amino acids with a branched side chain, namely L-leucine and L-isoleucine, as well as D-pantothenate.

Plasma metabolomics and gene regulatory networks analysis reveal the role of nonstructural SARS-CoV-2 viral proteins in metabolic dysregulation in COVID-19 patients.

Metabolomic analysis of blood plasma samples from COVID-19 patients is a promising approach allowing for the evaluation of disease progression. We performed the metabolomic analysis of plasma samples of 30 COVID-19 patients and the 19 controls using the high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometric detection (LC-MS/MS). In our analysis, we identified 103 metabolites enriched in KEGG metabolic pathways such as amino acid metabolism and the biosynthesis of aminoacyl-tRNAs, which differed significantly between the COVID-19 patients and the controls. Using ANDSystem software, we performed the reconstruction of gene networks describing the potential genetic regulation of metabolic pathways perturbed in COVID-19 patients by SARS-CoV-2 proteins. The nonstructural proteins of SARS-CoV-2 (orf8 and nsp5) and structural protein E were involved in the greater number of regulatory pathways. The reconstructed gene networks suggest the hypotheses on the molecular mechanisms of virus-host interactions in COVID-19 pathology and provide a basis for the further experimental and computer studies of the regulation of metabolic pathways by SARS-CoV-2 proteins. Our metabolomic analysis suggests the need for nonstructural protein-based vaccines and the control strategy to reduce the disease progression of COVID-19.

ANDVisio: a new tool for graphic visualization and analysis of literature mined associative gene networks in the ANDSystem.

The ANDVisio tool is designed to reconstruct and analyze associative gene networks in the earlier developed Associative Network Discovery System (ANDSystem) software package. The ANDSystem incorporates utilities for automated extraction of knowledge from Pubmed published scientific texts, analysis of factographic databases, also the ANDCell database containing information on molecular-genetic events retrieved from texts and databases. ANDVisio is a new user's interface to the ANDCell database stored in a remote server. ANDVisio provides graphic visualization, editing, search, also saving of associative gene networks in different formats resulting from user's request. The associative gene networks describe semantic relationships between molecular-genetic objects (proteins, genes, metabolites and others), biological processes, and diseases. ANDVisio is provided with various tools to support filtering by object types, relationships between objects and information sources; graph layout; search of the shortest pathway; cycles in graphs.

[Protein Structure Discovery: software package to perform computational proteomics tasks].

Software-information system Protein Structure Discovery was developed. The system can be used for the wide range of tasks in the field of computer proteomics including prediction of function, structure and immunological properties of proteins. A specially created section of the system allows evaluating the quantitative and qualitative effects of mutations on the structural and functional properties of proteins. There are 19 of different programs integrated into the system, including the database of protein functional sites PDBSite, a PDBSiteScan program for the prediction of functional sites in three-dimensional structures of proteins, and WebProAnalyst program for the quantitative analysis of the structure-activity relationship of proteins. Protein Structure Discovery program has a Web interface and is available for users through the Internet (http://www-bionet.sscc.ru/psd/). For example, binding sites of zinc ion and ADP showed high stability of the method to errors PDBSiteScan reconstruction of spatial structures of proteins in the recognition of functional sites in model structures.

[Evolutionary trends in the prokaryotic community and prokaryotic community-phage systems].

The Evolutionary Constructor software has been used for computer simulation of the life and evolution of communities of unicellular haploid organisms (prokaryotic cells). Opposite trends of the community evolution (simplification and complication of the genome) have been studied. It has been demonstrated that species with reduced genomes tend to replace genetically and metabolically rich species under highly favorable environmental conditions. Under unfavorable conditions, the opposite tendency is observed. It has also been shown that introduction of phages capable of killing the cells into the system may radically change the current evolutionary trend.