New drug discovery is based on the analysis of public information about the mechanisms of the disease, molecular targets, and ligands, which interaction with the target could lead to the normalization of the pathological process. The available data on diseases, drugs, pharmacological effects, molecular targets, and drug-like substances, taking into account the combinatorics of the associative relations between them, correspond to the Big Data. To analyze such data, the application of computer-aided drug design methods is necessary. An overview of the studies in this area performed by the Laboratory for Structure-Function Based Drug Design of IBMC is presented. We have developed the approaches to identifying promising pharmacological targets, predicting several thousand types of biological activity based on the structural formula of the compound, analyzing protein-ligand interactions based on assessing local similarity of amino acid sequences, identifying likely molecular mechanisms of side effects of drugs, calculating the integral toxicity of drugs taking into account their metabolism, have been developed in the human body, predicting sustainable and sensitive options strains and evaluating the effectiveness of combinations of antiretroviral drugs in patients, taking into account the molecular genetic characteristics of the clinical isolates of HIV-1. Our computer programs are implemented as the web-services freely available on the Internet, which are used by thousands of researchers from many countries of the world to select the most promising substances for the synthesis and determine the priority areas for experimental testing of their biological activity.
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Keywords: chemical-biological interactions, bioinformatics, chemoinformatics, ligand-based drug design, systems pharmacology
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Poroikov V.V. (2020) Computer-aided drug design: from discovery of novel pharmaceutical agents to systems pharmacology. Biomeditsinskaya Khimiya, 66(1), 30-41.
et al. Computer-aided drug design: from discovery of novel pharmaceutical agents to systems pharmacology // Biomeditsinskaya Khimiya. - 2020. - V. 66. -N 1. - P. 30-41.
et al., "Computer-aided drug design: from discovery of novel pharmaceutical agents to systems pharmacology." Biomeditsinskaya Khimiya 66.1 (2020): 30-41.
Poroikov, V. V. (2020). Computer-aided drug design: from discovery of novel pharmaceutical agents to systems pharmacology. Biomeditsinskaya Khimiya, 66(1), 30-41.
Hopkins A.L. (2008) in: The Practice in Medicinal Chemistry, fourth edition (Wermuth C.G., Aldous D., Raboisson P., Rognan D., eds.) Elsevier (Academic Press), Amsterdam a. o., p. 405. Scholar google search
ICD-11. Retrieved January, 2020, from https://icd.who.int/browse11/l-m/en. Scholar google search
Classification of diseases. Retrieved January, 2020, from https://www.britannica.com/science/human-disease/ Classifications-of-diseases. Scholar google search
Polishchuk P.G., Madzhidov T.I., Varnek A. (2013) J. Comput. Aided Mol. Des., 27(8), 675-679. CrossRef Scholar google search
Filimonov D.A., Poroikov V.V., Gloziozova T.A., Lagunin A.A. (2006) PASS program package, Russian State Patent Agency Certificate, No. 2006613275 of 15.09.2006. Scholar google search
Burov Yu.V., Poroikov V.V., Korolchenko L.V. (1990) National system for registration and biological testing of chemical compounds: facilities for new drugs search. Bull. Natl. Center for Biologically Active Compounds, No. 1, 4-25. Scholar google search
Filimonov D.A., Druzhilovskiy D.S., Lagunin A.A., Gloriozova T.A., Rudik A.V., Dmitriev A.V., Pogodin P.V., Poroikov V.V. (2018) Biomedical Chemistry: Research and Methods, 1(1), e00004. CrossRef Scholar google search
Lagunin A.A., Poroikov V.V., Filimonov D.A., Gloziozova T.A. (2006) PharmaExpert program package, Russian State Patent Agency Certificate, No. 2006613590 of 16.10.2006. Scholar google search
Koborova O.N., Filimonov D.A., Zakharov A.V., Lagunin A.A., Ivanov S.M., Kel A., Poroikov V.V. (2009) SAR QSAR Environ. Res., 20(7-8), 755-766. CrossRef Scholar google search
Koborova O.N., Filimonov D.A., Kel A.E., Poroikov V.V. (2011) NetFlowEx program package, Russian State Patent Agency Certificate, No. 2011617330 of 21.09.2011. Scholar google search
Ivanov S.M., Filimonov D.A., Lagunin A.A., Poroikov V.V. (2011) Net2Target program package, Russian State Patent Agency Certificate, No. 2014660877 of 17.10.2014. Scholar google search
Koborova O.N., Filimonov D.A., Zakharov A.V., Lagunin A.A., Kel A., Kolpakov F., Sharipov R., Kondrachin Y., Poroikov V.V. (2009) The Herald of Vavilov Society for Geneticists and Breeding Scientists, 13(1) 201-207. Scholar google search
ChemNavigator. Retrieved January, 2020, from www.chemnavigator.com. Scholar google search
White R.E. (2012) in: Encyclopedia of Drug Metabolism and Interactions. Vol. 1. (Lyubimov A.V., ed.) Wiley, Weinheim a.o., p.p. 3-42. Scholar google search
Dmitriev A., Rudik A., Filimonov D., Lagunin A., Pogodin P., Dubovskaja V., Bezhentsev V., Ivanov S., Druzhilovsky D., Tarasova O., Poroikov V. (2017) Pure Appl. Chem., 89(10), 1449-1458. CrossRef Scholar google search
Tarasova O., Filimonov D., Poroikov V. (2016) J. Bioinform. Comput. Biol., 15(2), 1650040 1 14. CrossRef Scholar google search
Tarasova O., Biziukova N., Kireev D., Lagunin A., Ivanov S., Filimonov D., Poroikov V. (2020) Int. J. Mol. Sc., 21(3), 748. CrossRef Scholar google search
Liu E.T., Lauffenburger D.A. (eds.) (2009) Systems Biomedicine. Concepts and Perspectives. Elsevier, Amsterdam et al., 448 p. Scholar google search
Mager D.E., Kimko H.H.C. (eds.) (2016) Systems Pharmacology and Pharmacodynamics. Springer, Basel et al., 511 p. CrossRef Scholar google search
von Eichborn J., Murgueitio M.S., Dunkel M., Koerner S., Bourne P.E., Preissner R. (2011) Nucl. Acids Res., 39(Database issue), D1060-D1066. CrossRef Scholar google search
Huang R., Southall N., Wang Y., Yasgar A., Shinn P., Jadhav A., Nguyen D.-T., Austin C.P. (2011) Sci. Transl. Med., 3(80), 80ps16. CrossRef Scholar google search
Santos R., Ursu O., Gaulton A., Bento A.P., Donadi R.S., Bologa C.G., Karlsson A., Al-Lazikani B., Hersey A., Oprea T.I., Overington J.P. (2017) Nat. Rev. Drug Discov., 16(1), 19-34. CrossRef Scholar google search
Nguyen D.T., Mathias S., Bologa C., Brunak S., Fernandez N., Gaulton A., Hersey A., Holmes J., Jensen L.J., Karlsson A., Liu G., Ma'ayan A., Mandava G., Mani S., Mehta S., Overington J., Patel J., Rouillard A.D., Schürer S., Sheils T., Simeonov A., Sklar L.A., Southall N., Ursu O., Vidovic D., Waller A., Yang J., Jadhav A., Oprea T.I., Guha R. (2017) Nucl. Acids Res., 45(D1), D995-D1002. CrossRef Scholar google search
Carvalho-Silva D., Pierleoni A., Pignatelli M., Ong C.K., Fumis L., Karamanis N., Carmona M., Faulconbridge A., Hercules A., McAuley E., Miranda A., Peat G., Spitzer M., Barrett J., Hulcoop D.G., Papa E., Koscielny G., Dunham I. (2019) Nucl. Acids Res., 47(D1), D1056-D1065. CrossRef Scholar google search
Ursu O., Holmes J., Bologa C.G., Yang J.J., Mathias S.L., Stathias V., Nguyen D.T., Schürer S., Oprea T. (2019) Nucl. Acids Res., 47(D1), D963-D970. CrossRef Scholar google search
