In this work, thymomimetic vilon (Lys-Glu) was studied by molecular modeling methods. Conformational profiles of the dipeptide were studied in the framework of molecular mechanics, electronic characteristics were analyzed using quantum chemical calculations, and molecular docking of the studied ligand with a T-cell receptor was carried out. The energy and geometric parameters of stable structures of the molecule, the effective charges of atoms, the population coefficients of atomic orbitals, the dipole moment, the energies of the highest occupied molecular orbital and the lowest unoccupied molecular orbital, the energy gap, contours and electrostatic potential maps are calculated. It was found that in the folded conformation, the side chains of the lysine and glutamic acid residues interact more efficiently than in the unfolded conformation, which leads to the formation of a salt bridge between the N atom of the amino group of the Lys side chain and the O atoms of the carboxyl group of the Glu side chain. It was shown that this structure is more stable in electronic parameters, and also well complements the cleft on the surface of a specific receptor, forming a stable complex, characterized by a high binding energy. The data obtained allowed us to evaluate folded structure as the biologically active conformation of vilon. The results of the study provide an improved description of the structural and functional relationships of the thymomimetics.
molecular mechanics, quantum chemistry, molecular docking, vilon, bioactive conformation
1. Havinson V.H., Anisimov V.N. Peptidnye bioregulyatory i starenie. SPb.: Nauka, 2003, 223 s. @@[Khavinson V.Kh., Anisimov V.N. Peptide bioregulators and aging. SPb.: Nauka, 2003, 36 p. (In Russ.)]
2. Khavinson V.Kh., Kuznik B.I., Ryzhak G.A., Peptide Bioregulators: A New Class of Geroprotectors, Report 2. The Results of Clinical Trials. Advances in Gerontology, 2014, vol. 4, no. 4 pp. 346-361.
3. Akverdieva G.A. Demukhamedova S.D., Godjayev N.M. Theoretical study of thymomimetic peptide H-Lys-Glu-OH (Vilon) and its complex with the receptor. Conference proceedings “Modern Trends in Physics”, Baku 01-03 May, 2019, ISSN 2522-4352, pp. 165-169
4. Godzhaev N.M., Maksumov I.C., Ismailova L.I. Programma poluempiricheskogo rascheta konformaciy molekulyarnyh kompleksov. Zhurnal strukturnoy himii, 1983, t. 24, № 4, s.147-148. @@[Godjayev N.M., Maksumov I.S., Ismailova L.I. Program of semiempirical calculations of conformations of molecular complexes. Jurnal Structurnoy Chimii, 1983, vol. 24, no. 4, pp. 147-148. (In Russ.)]
5. Akverdieva G.A., Godjayev N.M. Improvement of program of calculation of molecular conformation. J. Modern Technology & Engineering, 2017, vol. 2, pp. 140-145.
6. Allinger N.L.,Yuh Y., QCPE 395, Quantum chemistry program exchange, Indiana Univ., Indiana, 1982.
7. Trott O., Olson A. J., AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading, Journal of Computational Chemistry, 2010, vol. 31, pp. 455-461, DOI:https://doi.org/10.1002/jcc.21334.
8. DeLano W.L. The PyMOL molecular graphics system, 2010, URL: http://www.pymol.org.
