Biomedical subjects

V I Fomin

Publications and source records attributed to V I Fomin.

5 recordsLinked to original sources

PubMed1995

PROANAL version 2: multifunctional program for analysis of multiple protein sequence alignments and for studying the structure--activity relationships in protein families.

A new version of the program PROANAL is described. A multiple linear regression analysis of the protein structure--activity relationship allows one to investigate the combinations of protein sites and factors influencing the activity. The program also provides the possibility to seek out protein sites, conservative or variable in variations of physicochemical characteristics, and regions with high or low values of these characteristics. PROANAL2 may be useful in the simulation of protein-engineering experiments and in the search of a number of protein regions such as functional sites, secondary structures, solvent-exposed regions, T- and B-cell antigenic determinants, etc.

Algorithms↗

PubMed1993

Algorithm and computer program Pro__Anal for analysis of relationship between structure and activity in a family of proteins or peptides.

In this paper we introduce a computer algorithm and program Pro__Anal for analysis of the structure-activity relationship in a family of evolutionarily related (and/or artificially mutated) proteins/peptides. The program uses aligned amino acid sequences with data of their activity (pK, Km, ED50 or any other) and searches for correlations between data on activity and various physico-chemical characteristics of different regions in primary structures. In automatic mode, the program generates and verifies hypotheses on the disposition of a sequential modulating region in a protein, and key characteristics of the region. In manual mode, users can generate and analyze their own hypotheses. The program is implemented on IBM PC or compatible computers. It is designed to be easily handled by the occasional computer user and yet it is powerful enough for experienced professionals. Pro__Anal operation is demonstrated on the example of finding modulating centers in a family of disintegrins-proteins from snake venoms which inhibit fibrinogen interaction with platelet receptors. In another example it is shown that the immunogenicity of peptides is connected with their positive charge.

Algorithms↗

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↗

PubMedDate not supplied

[Development of rules for vaccine engineering based on the variability of peptide fragments in closely related proteins].

Based on the protein sequence data bank (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" of 383 protein pairs. Amino acid residues composition of "variable fragments" was examined and indexes of potential amino acid residues variability was formed. An analysis of amino acid fragments replaceability was carried out by substituting the N-, C-terminal, or middle part of a chain), the fragments length differences and physico-chemical properties of residues, such as volume, hydrophobicity, polarity, isoelectric point, etc. Some general empirical rules of peptide insertions in carrier-proteins were created based on these analyses. The rules are directed for performing modifications maintaining the common structure and function of the carrier-protein molecule. The selection scheme for determining the regions suitable for modification and the criteria for defining the width of acceptable modifications in this regions were suggested. The use of potential variability profile for detecting regions suitable for peptide insertion was considered on the model of hepatitis B surface protein.

Amino Acid Sequence↗

PubMedDate not supplied

[Analysis of peptide fragment insertions in the basic proteins of the bacteriophage M13, f1, and fd envelopes. Interconnection of structural characteristics of the envelope protein and viability of mutant phages].

An analysis of 12 peptide fragment insertions into the major coat protein (protein pVIII) of bacteriophages M13, f1 and fd has been done. To elucidate the relations between protein structural characteristics and viability of mutant phages, we used the program Pro-Anal. Correlations were found between phage viability and different physicochemical and structural characteristics of protein N-termini. Thus peptide insertions in nonviable phages have high indexes of alpha-helicity, volumes, and polarity as well as high moments (alpha-helical and beta-structural) of isoelectric point. On the other hand, high beta-turn indexes are correlated with viability. The most important factor which determines phage viability is the lack of positively charged amino acid residues on the C-terminal ends of peptide insertions. The correlations found hold for the pVIII proteins of four related phages-M13, IKe, If1 and I2-2. Based on these results, the rule of obtaining viable mutant phages with insertions in the major coat protein is suggested. A new site is described for peptide insertions--upstream of the first amino acid residue of the mature protein sequence.

Amino Acid Sequence↗