Search academic texts

Information × Registration Number 0220U104608, 0120U105317 , R & D reports Title Rational design of acetylcholine muscarinic receptor inhibitors as potential components of combination therapy of chronic obstructive pulmonary disease (COPD) and asthma. popup.stage_title Head Nyporko Oleksii Y., Кандидат біологічних наук Registration Date 23-12-2020 Organization Taras Shevchenko National University of Kyiv popup.description2  The object of study - muscarinic receptors of acetylcholine M3 and M2. Purpose of work To test, optimize and standardize protocols of structural analysis in silico, virtual screening, biological testing and chemical optimization for their further use during the project. Reconstruct the spatial structure of mAChRs, analyze in detail the features of its surface and search for binding sites of organic compounds. Research methods - structural analysis in silico, molecular reconstruction, strain gauge analysis, molecular docking, conformational analysis. The protocols of structural analysis in silico, in particular, conformational analysis with detailed physicochemical characteristics of ligands, were developed and optimized, special attention was paid to the identification and energy of hydrogen bonds, which will provide a qualitative approach to rational design of acetylcholine receptor muscarinic inhibitors. The hardware for high-bandwidth virtual screening has been configured and the molecular docking protocol has been debugged with the AutoDock software package based on the bash script that will be used for the screening procedure. Using the registration and analysis of concentration-effect curves for known agonists and antagonists of muscarinic acetylcholine receptors, the development, optimization and standardization of protocols for biological testing of compounds - potential inhibitors of muscarinic acetylcholine receptors. A strategy for optimizing inhibitor compounds has been developed, which includes both optimizing the activity of the compounds and optimizing the physicochemical properties of these compounds, which is an important factor for the further use of the developed compounds to develop drugs based on them. For the first time the spatial structure of full-size muscarinic acetylcholine receptors M3 and M2 was reconstructed. Product Description popup.authors Bdzhola Volodymyr G. Voiteshenko Ivan S. Protopopov Mykola V. Starosyla Serhiy А. Tsymbaliuk Olha V. popup.nrat_date 2020-12-23 Close