Rational in silico design of aptamers for organophosphates based on the example of paraoxon |
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| Institution: | 1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Torez 44, St. Petersburg 194223, Russia;2. Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilova str., Moscow 119334, Russia;3. Leicester School of Allied Health Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK;4. Research Institute of Hygiene, Occupational Pathology and Human Ecology, bld.93 p.o.Kuz’molovsky, Leningrad Region 188663, Russia;1. Department of Mathematics and Physics,” Ennio de Giorgi”, University of Salento, Via Monteroni, Lecce, I-7310, Italy;2. Department of Chemistry, University of Bari, Via Orabona 4, Bari, I-70126, Italy;3. Department of Innovation Engineering, University of Salento, Via Monteroni, Lecce, I-73100, Italy;1. Analysis and Test Center of Chinese Academy of Tropical Agricultural Sciences, Haikou, 571101, China;2. Laboratory of Quality & Safety Risk Assessment for Tropical Products (Haikou) Ministry of Agriculture, Haikou, 571101, China;1. Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, Beijing Laboratory for Food Quality and Safety, 100193, Beijing, People’s Republic of China;2. Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, 410125, Changsha, People’s Republic of China;3. Key Laboratory of Molecular Epidemiology of Shenzhen, Shenzhen Center for Disease Control and Prevention, 518020, Shenzhen, People’s Republic of China;1. State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China;2. Hunan Provincial Key Lab of Dark Tea and Jin-Hua, School of Materials and Chemical Engineering, Hunan City University, Yiyang 413000, China;3. Hunan Key Laboratory of Biomedical Nanomaterials and Devices, Hunan University of Technology, Zhuzhou 412007, China;1. Institute of Biomedical Chemistry RAMS, Pogodinskaya str., 10, Moscow 119121, Russia;2. Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, Kuprevich str., 5/2, Minsk 220141, Belarus |
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| Abstract: | Poisoning by organophosphates (OPs) takes one of the leading places in the total number of exotoxicoses. Detoxication of OPs at the first stage of the poison entering the body could be achieved with the help of DNA- or RNA-aptamers, which are able to bind poisons in the bloodstream. The aim of the research was to develop an approach to rational in silico design of aptamers for OPs based on the example of paraoxon. From the published sequence of an aptamer binding organophosphorus pesticides, its three-dimensional model has been constructed. The most probable binding site for paraoxon was determined by molecular docking and molecular dynamics (MD) methods. Then the nucleotides of the binding site were mutated consequently and the values of free binding energy have been calculated using MD trajectories and MM-PBSA approach. On the basis of the energy values, two sequences that bind paraoxon most efficiently have been selected. The value of free binding energy of paraoxon with peripheral anionic site of acetylcholinesterase (AChE) has been calculated as well. It has been revealed that the aptamers found bind paraoxon more effectively than AChE. The peculiarities of paraoxon interaction with the aptamers nucleotides have been analyzed. The possibility of improving in silico approach for aptamer selection is discussed. |
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| Keywords: | Aptamer Molecular docking Molecular dynamics Rational design Organophosphates |
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