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Biomedical subjects

V A Kulichkov

Publications and source records attributed to V A Kulichkov.

At least 19 recordsLinked to original sources
PubMed1997

A bank of protein family patterns for rapid identification of possible functions of amino acid sequences.

A method and software tool to develop patterns of protein families has been designed. These patterns are intended for the identification of local similarities in arbitrary amino acid sequences with proteins of the SWISS-PROT bank. The method is based on the physical, chemical and structural properties of amino acids. It assembles a 'best set' of elements (a pattern) for a given group of aligned related proteins. These elements provide discrimination between proteins of a family and representatives of other families or random sequences. The method combines the advantages of BLOCKS (automatic generation of multiple elements for protein groups), PROSITE (simplicity of element presentation) and matrices/profiles (different distinctions between amino acids for different positions of aligned sequences). Using our method, a data bank of protein family patterns, PROF_PAT, is produced. This data bank is based on the 27,752 amino acid sequences of SWISS-PROT bank release 24. The characteristics of patterns of 743 related protein groups are described. The results of comparisons of PROF_PAT patterns with the proteins of the SWISS-PROT bank are discussed.

Algorithms↗
PubMed1995

A computer system for analysis and integrated description of regulation of the molecular-genetic system of interferon induction and action.

A new theoretical approach to elaboration of an information-analytical integrated knowledge base containing data on regulation and function of biological systems is presented. The knowledge base incorporates: (i) a reference database containing experimental data on the structural-functional organization of a biological system; (ii) a dynamic mathematical model for analysis of the evolution of the system over time; and (iii) an interpretation module of simulation results. Application of this approach to theoretical investigation of the interferon system in the case of viral infection is discussed. The approach is specific in that it uses mathematical modeling technology, which allows one to generate mathematical models of different degrees of complexity in the analysis of the diverse aspects of biological system behavior. This approach allows one not only to store and to treat available experimental data, but also to acquire new knowledge about the behavior of a biological system. The proposed approach is implemented as a computer system for the IBM PC and compatibles.

Algorithms↗
PubMed1991

Mathematical model of antiviral immune response regulation. II. Mathematical formalization of the modelled processes. Imitation of acute course of hepatitis B.

The mathematical formalization of the conceptual model for antiviral immune response regulation described in the preceding report was carried out. The mathematical model is presented as a system of 30 ordinary nonlinear differential equations with delays. The algorithm for numerical integration of the mathematical model is based on Gear's methods of variable step and variable order. Initial conditions and parameters, as well as intervals of plausible values for them, were chosen for adaptation of the model for description of acute hepatitis B.

Acute Disease↗
PubMed1990

Protein fragment variability analysis and some principles of protein engineering of vaccines.

Based on protein sequence databank (PIR), the 'variable fragment' bank, comprising pairs of closely-related proteins, containing one or more strongly differing sites of primary structures, was formed. The bank includes 465 'variable fragments' in 383 protein pairs. The amino acid composition of 'variable fragments' was examined and indices of potential amino acid residue variability were formed. An analysis of the interchangeability of amino acid fragments depending on the substitution site (N- or C-terminal, or middle part of a chain), the fragment length differences and physico-chemical properties of residues, such as volume, hydrophobicity, polarity and isoelectric point, was carried out. Based on this analysis some general empirical rules of peptide insertions in carrier proteins were created. The rules are directed at performing modifications leaving the general structure and function of the carrier protein molecule unchanged. The selection scheme for the regions suitable for modification and the criteria for determination of the range of acceptable variations in these regions were suggested. The use of the potential variability profile for detecting regions suitable for peptide insertion was considered using surface protein of hepatitis B virus as an example.

Amino Acid Sequence↗
PubMed1987

[Formation and properties of artificial polycistrons containing truncated genes for E. coli tryptophan operon and phage M13 envelope protein].

Using gene fragments encoding the leader peptide of E. coli tryptophane operon (as duplicated fragment HhaI-140) or M13 phage coat protein (as TaqI-381 or HaeIII-1623 fragments) and basing on pDS1 family of plasmids, expression vectors have been constructed which contained transcription promoters Ptrp, PVIII, and Pv + PVIII, respectively. An artificial gene for human leukocyte interferon alpha 2 (ifn-alpha 2) has been cloned into these plasmids, so that its transcription was a part of polycistronic mRNA and preceding translation was terminated upstream to the ribosome binding site and starting codon of the interferon gene. E. coli cells harbouring these recombinant plasmids provided high level of the interferon biosynthesis. The effect of the mRNA length on the amount of protein synthesised under control of the M13 coat protein transcription-translation signals has been found.

Base Sequence↗
PubMed1987

[Duplication of a synthetic gene for human leukocyte interferon and its expression in polycistron mRNA with coupled translation system].

Using a chemically synthesised adapter, the coding part of an artificial gene for human leukocyte alpha 2 interferon (ifn-alpha 2) has been duplicated. The adapter contained a termination signal of the first gene (TAA) within the Shine-Dalgarno sequence of the second gene (TAAGGA), distance between the terminating codon and starting codon of the second gene being 11 nucleotides. In another case this distance was 69 nucleotides, with the same SD sequence. The expression of the tandems as a part of polycistrons has been studied under control of promoters Plac, (Ptrp)2 of E. coli, and PVIII of M13 phage. It was found that tandems of ifn-alpha 2 genes in polycistronic structures trp L-ifn-ifn and IX-VIII-ifn-ifn under control of promoters (Ptrp)2 and PVIII, respectively, provided high level of the interferon biosynthesis, thus differing from the tandem under Plac promoter control, which had only ifn-ifn translation coupling.

Escherichia coli↗
PubMed1987

[Rapid automated synthesis on paper disks of oligodeoxyribonucleotides constituting the promoter fragment of the vaccinia virus genome].

For automation of segmental solid-phase synthesis a simple approach leading to the optimal scheme of synthesis of a large numbers of oligonucleotides in one reaction vessel has been proposed. An advantage of the scheme as compared with synthesis in four reaction vessels is a lower number of condensation steps and increased economy of the process. Sixteen oligodeoxyribonucleotides constituting promoter fragment of the viral genome have been synthesised by the modified segmental method on "Victoriya-2" synthesizer according to the optimal scheme.

Base Sequence↗
PubMed1978

Analysis of mechanisms regulating the expression of parental alleles at the GPD locus in mule erythrocytes.

Erythrocyte glucose-6-phosphate dehydrogenase (G6PD) was examined by 13% starch gel electrophoresis in 74 mules (42 females and 32 males), 35 donkeys, and ten horses. The quantitative expression of the parental alleles at the Gpd locus varies greatly in female mules from the hemizygous expression of the maternal allele to that of the paternal. The data obtained indicate that the X chromosomes are randomly inactivated in females mules. No selective advantage of a cell population with a maternally (or paternally) derived X active was found in female mule erythrocytes. It is suggested that the phenotypic variability in the expression of the parental Gpd alleles is related to the random proportions established between cells having either a maternal or paternal X active in an initiator (stem) cell group giving rise to erythroid tissue. Initiator cell numbers estimated for erythroid tissue (six or seven) are close to those reported for human females and intergeneric fox hybrids. These numbers may vary depending on the duration of the time of determination and the division rate of initiator cells at determination.

Alleles↗
PubMed1978

Allelic expression in intergeneric fox hybrids (Alopex lagopus x Vulpes vulpes). III. Regulation of the expression of the parental alleles at the Gpd locus linked to the X chromosome.

The electrophoretic pattern of glucose-6-phosphate dehydrogenase (G6PD) was studied in 60 intergeneric fox hybrids (Alopex lagopus x Vulpes vulpes), 33 females and 27 males. It is shown that the structural gene for G6PD, designated Gpd, is located on the X chromosome in both Arctic and silver foxes. Analysis of G6PD patterns in the erythrocytes of hybrid females demonstrated that the phenotypic expression of parental alleles at the Gpd locus varied considerably: from 1:1 to the hemizygous manifestation of an allele of either the Artic or the silver fox. The expression of the parental alleles at this locus is different in the various tissues of single female hybrids. It is suggested that the variable quantitative expression of the alleles at the Gpd locus in hybrid females is related to the presence of two cell populations having in an active state either the X chromosome of the Arctic fox or that of the silver fox. It is also proposed that the size of the two cell populations is largely affected by the different relationships between cells having different activated X-chromosomes among initiator (stem) cells from which various definitive organs and tissues develop. The number of initiator cells for erythroid tissue has been calculated to be five or six.

Alleles↗
PubMed1976

[Expression of homologous genes in interspecies arctic fox x silver fox hybrids (Alopex lagopus X Vulpes vulpes). III. Mechanisms of expression of alleles of locus GPD, located on the X-chromosome].

The electrophoretic pattern of glucose-6-phosphate dehydrogenase (G-6-PD) was studied in 60 intergeneric fox hybrids (Alopex lagopus X Vulpes vulpes), 33 females and 27 males. It is shown that the structural gene for G-6-PD, designated as Gpd, is located on the X-chromosome in both Arctic and silver foxes. Analysis of G-6-PD in the erythrocytes of hybrid females demonstrated that the phenotypic expression of parental alleles at the locus Gpd varied considerably: from 1:1 to the hemizygous manisfestation of an allele of either the Arctic or silver fox. It is suggested that the variable quantitative expression of the alleles at the locus Gpd in hybrid females is related to the presence of two cell populations having in an active state either the X-chromosome of the Artic or silver fox. It is also assumed that the size of two cell populations is significantly influenced by the different relations in the group of initiator (stem) cells, which possess different X-chromosomes in an active state, which has been established in early embryogenesis. In the case of erythrocytes, it is found that the number of initiator (stem) cells for erythrocytes comprises 5-6.

Alleles↗