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M A Rodionov

Publications and source records attributed to M A Rodionov.

12 recordsLinked to original sources
PubMed1998

Sequence and structure conservation in a protein core.

In order to study structural aspects of sequence conservation in families of homologous proteins, we have analyzed structurally aligned sequences of 585 proteins grouped into 128 homologous families. The conservation of a residue in a family is defined as the average residue similarity in a given position of aligned sequences. The residue similarities were expressed in the form of log-odd substitution tables that take into account the environments of amino acids in three-dimensional structures. The protein core is defined as those residues that have less then 7% solvent accessibility. The density of a protein core is described in terms of atom packing, which is investigated as a criterion for residue substitution and conservation. Although there is no significant correlation between sequence conservation and average atom packing around nonpolar residues such as leucine, valine and isoleucine, a significant correlation is observed for polar residues in the protein core. This may be explained by the hydrogen bonds in which polar residues are involved; the better their protection from water access the more stable should be the structure in that position.

Amino Acid Sequence↗
PubMed1994

The recognition of protein structure and function from sequence: adding value to genome data.

The explosion of DNA sequence data from genome projects presents many challenges. For instance, we must extend our current knowledge of protein structure and function so that it can be applied to these new sequences. The derivation of rules for the relationships between sequence and structure allow us to recognize a common fold by the use of tertiary templates. New techniques enable us to begin to meet the challenge of rule-based modelling of distantly related proteins. This paper describes an integrated and knowledge-based approach to the prediction of protein structure and function which can maximize the value of sequence information.

Amino Acid Sequence↗
PubMed1994

Residue-residue contact substitution probabilities derived from aligned three-dimensional structures and the identification of common folds.

We report the derivation of scores that are based on the analysis of residue-residue contact matrices from 443 3-dimensional structures aligned structurally as 96 families, which can be used to evaluate sequence-structure matches. Residue-residue contacts and the more than 3 x 10(6) amino acid substitutions that take place between pairs of these contacts at aligned positions within each family of structures have been tabulated and segregated according to the solvent accessibility of the residues involved. Contact maps within a family of structures are shown to be highly conserved (approximately 75%) even when the sequence identity is approaching 10%. In a comparison involving a globin structure and the search of a sequence databank (> 21,000 sequences), the contact probability scores are shown to provide a very powerful secondary screen for the top scoring sequence-structure matches, where between 69% and 84% of the unrelated matches are eliminated. The search of an aligned set of 2 globins against a sequence databank and the subsequent residue contact-based evaluation of matches locates all 618 globin sequences before the first non-globin match. From a single bacterial serine proteinase structure, the structural template approach coupled with residue-residue contact substitution data lead to the detection of the mammalian serine proteinase family among the top matches in the search of a sequence databank.

Amino Acid Sequence↗
PubMed1993

[Monoclonal antibodies to human spleen ferritin. II. Localization of epitopes and quantitative parameters of antigen binding].

The interaction of three monoclonal antibodies with human spleen ferritin has been studied. Using titration of various monoclonal antibody-containing media with the immobilized antigen, the specific content of active antibodies capable of binding to ferritin was determined, which was 22-27% for ascitic fluids, 35-50% for total mouse IgG and 88% for affinity-purified HSF102 antibody. Using [125I]ferritin and a novel computer-aided technique for determining the antigen-antibody binding, the affinity constants were obtained which ranged from 6.10(8) to 3.10(9) M-1. The monoclonal antibodies inhibited by 77-95% the binding of rabbit polyclonal antibodies to ferritin. This result is suggestive of a compact distribution on the ferritin surface of immunodominant epitopes forming clusters of closely related antigenic sites recognized by monoclonal and rabbit polyclonal antibodies. Competitive binding and additivity assays revealed that the epitope for the HSF102 antibody was sterically remote from the epitopes recognized by HSF101 and HSF103 antibodies to allow for noncompetitive binding of two different monoclonal antibodies. The competition between HSF101 and HSF103 antibodies pointed to the overlapping of their epitopes. It was found that no more than four [125I]IgG molecules could simultaneously be bound to one ferritin molecule which reflected the maximal valency of this antigen during its interaction with IgG antibodies.

Antibodies, Monoclonal↗
PubMed1989

[Chemical modification of antibodies against carcino-embryonal antigen].

Chemical modification of different amino acid residues and the carbohydrate moiety of antibodies to carcino-embryonic antigen (CEA) was used to elucidate their role in the interaction with CEA and to evaluate the effect of antibody modification and steric factor in immunosorbent synthesis. The distribution of the modified groups among the structural fragments of IgG and the levels of changes in the antigen-binding properties of modified antibodies were investigated. The Fc-fragment of IgG was shown to contain carboxylic groups, tyrosine and histidine residues, whose modification influences the antigen-binding properties as a result of generalized conformational changes in the IgG molecule. A comparison of these results with earlier obtained data on the functional properties, of immobilized antibodies revealed that the decrease of antigen-binding characteristics of anti-CEA after IgG immobilization via NH2- and COOH-groups, carbohydrate moiety, tyrosine and histidine residues is due to the direct effect of antibody modification, whereas the changes in parameters of antibody interaction with antigen after IgG immobilization via SH-groups, methionine and histidine residues is due to steric hindrances.

Amino Acids↗
PubMed1988

[Optimization of methods of immobilization of anti-immunoglobulins. Equilibrium parameters of the interaction of immobilized antibodies with an antigen].

Methods for immobilization of anti-immunoglobulins on insoluble supports were optimized, and the interaction of immunoadsorbents obtained with [125I]-labeled rabbit IgG was investigated. It was shown that this interaction can be adequately described by a rather simple equilibrium model which reflects the interaction of a monovalent antigen with two independent types of binding sites. Within the framework of this model the association constants as well as the concentrations of high affinity binding sites which influence the capacity and efficiency of the separation system were determined. Optimization of the immobilization methods implicated a study on the role of certain functional groups of the antibody involved in the formation of covalent bonds, on the effect of the spacer arm length on the properties of immobilized antibody as well as on the role of the degree of immobilization. It was found that immunoadsorbents obtained after antibody immobilization via lysine or tyrosine residues on matrices with a specific spacer group are the optimal ones.

Animals↗
PubMed1987

Prediction of exposure degree diagram and sites of limited proteolysis in globular proteins as an approach to computer-aided design of protein bioregulators with prolonged action.

In order to prolong the lifetime of protein bioregulators in blood it is possible to engineer analogs with protected sites of limited proteolysis. To determine the sites, primarily accessible to trypsin-like proteases, a computer procedure has been developed, including a prediction algorithm, to produce the residue diagram of a globular protein and a discriminant algorithm to determine the sites most liable to proteolysis. The accuracy of prediction of amino acid residue exposure is characterised by correlation coefficients between experimental and theoretical exposure values, the coefficients being about 0.7 as calculated for 10 globular proteins. The classification of Arg and Lys residues into two groups, susceptible or insusceptible to protease, has an error percentage of about 25.

Arginine↗
PubMedDate not supplied

[Prognosis of the degree of exposure of amino acid residues in globular proteins in relation to various problems of protein engineering].

The algorithm was developed to predict the degree of exposure of amino acid residues in globular proteins. This algorithm combined with standard discriminant analysis methods was used for evaluation of the accessibility of Lys and Arg residues for trypsin-like proteases attack. The procedure can be useful for a computer-aided design of prolonged-action protein drug preparations.

Amino Acids↗
PubMedDate not supplied

[Analysis of the spatial structure of proteins in terms of residue-residue contacts. II. Contact affinity].

The possibility of detecting the mutual amino acid residue affinity when protein three-dimensional structures are described in terms of residue-residue contact matrices is discussed. The hypothesis of the lack of affinity between amino acid residues is examined; the values of the pertinent elements of the overall residue-residue contact matrices prove not to be statistically different from random estimates in 91%; the chance hypothesis is rejected in 9% of cases, represented as a rule by residues with charged side groups, especially oppositely charged ones.

Amino Acids↗