Modeling and interaction analysis of the tumor necrosis factor-alpha with oligopeptides

The aim of the study was the design, characteristics and analysis of the TNFα interaction with oligopeptideanalogs of the interaction site of TNFα with TNFα-R2. Here are the results of the analysis contact zone of TNFα with TNFα-R2, determination of the potentially most effective oligopeptides, study of the binding free energy of oligopeptides and its changes depending on the number of amino acid residues in the peptide chain, as well as the TNFα form (monomer or trimer). Here are described the most typical loci of oligopeptides interaction with cytokine. To confirm the calculations, the effectiveness of the selected oligopeptides was evaluated in experiments in vitro.For visualization of the molecular complex and work with the pdb file we are used Chimera 1.14 software with AutoDocVina utility. For in vitro studies, were used indirect enzyme immunoassay reagent kits. The initial concentration of oligopeptides is 10 µM, the initial concentration of TNFα (×10–8): 0; 0.0287; 0.0862; 0.2300; 0.5750; 1.4370 µM. When oligopeptides interact with mTNFα, the binding efficiency increase was observed with an increase in the number of amino acid residues in the chain. With tTNFα, such dependence was not observed. A statistically significant difference was  observed in the binding energy of di-, tri-, and tetra peptides with mTNFα, with tTNFα, the differences found were not statistically significant.Thus, the data were obtained, which allowed us to come to the following conclusions: 1) the energy of interaction of oligopeptides with tTNFα does not depend on the number of amino acid residues in the oligopeptide; 2) the trimerized form of TNFα interacts most effectively with oligopeptides in comparison with mTNFα; 3) oligopeptides containing the -Trp- and being a spatial analogue of the TNFα-R2 fragment (-Trp65-Asn66-Trp67-Val68-Pro69-) interact most effectively; 4) it was selected three oligopeptides are the most promising for the binding of TNFα. The experiments in vitro confirmed the effectiveness only one oligopeptide