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Анализ in silico вероятных зависимостей «структура-активность» этанола
Introduction. The active integration of rapidly developing omics and computer technologies in the 21st century has led to a breakthrough in understanding the principles of the functioning of living systems. One of the dynamically developing integrative areas in biology is biological modeling. The fundamental paradigm has been the methodology that allows for the prediction of the biological activity of molecules based on the analysis of their Structure-Activity Relationship (SAR).
The goal of this work is to predict the marketing potential of ethanol's involvement in parametabolic interactions, which is relevant for a deeper understanding of its biological activity at the molecular level.
Material and Methods. To gain a deeper and more detailed understanding of biological processes, the Prediction of Activity Spectra for Substances (PASS) program was used, which allows for the exploration of the structure, conformational properties, and dynamics of biomolecule interactions. The forecast is analyzed based on the probabilities of presence (Pa) or absence (Pi) of each type of biological activity, with calculated quantitative estimates ranging from 0 to 1.
Results. The object of our study is the small molecule ethanol, which is an active and indispensable participant in basic metabolism and is generally involved in maintaining homeostasis in the body. The obtained forecast results indicate that ethanol can exhibit such pharmacological effects as hem-atotropic (Ra 0.886), antiviral (Ra 0.776), membranotropic (Ra 0.775), antihypoxic (Ra 0.744) and many others. The forecast shows that ethanol affects the metabolism of carbohydrates, lipids, and proteins, and has the most significant effect on carbohydrate metabolism. It has a high probability of inhibiting the activity of transketolase (0.743), pyruvate decarboxylase (Ra 0.705), and malate dehydrogenase (Ra 0.643). Ethanol can modulate the activity of enzymes located in the cell membrane, such as phosphatidate phosphatase (Ra 0.852), ethanolamine phosphate transferase (Ra 0.701), and H/K ATPase (Ra 0.703). The probable molecular mechanisms of action of ethanol known to be a stimulator of the release of serotonin (Pa 0.641) and histamine (Pa 0.563).
Conclusion. Ethanol is a small molecule with an exceptionally simple chemical structure, and it can exhibit a variety of pharmacological effects and molecular mechanisms of action, such as enzyme inhibition/activation, neurotransmitter release stimulation, and other activities. Although some biological properties of ethanol confirmed experimentally, others require further study, but they certainly lay the foundation for further research on the effects of ethanol on biological systems.