USE OF IN SILICO RESEARCH METHODS TO PREDICT PHARMACOKINETIC PROPERTIES AND SEARCH OF THE BIOLOGICALLY ACTIVE SUBSTANCES
DOI:
https://doi.org/10.11603/2312-0967.2024.3.14868Keywords:
molecular docking, in silico research, virtual screening, affinity, intermolecular interaction, binding site, ligandAbstract
The aim of the work. Conduct a review of computer programs, software packages, and databases that are appropriate to use for conducting in silico research for the purpose of predicting pharmacokinetic properties and searching for biologically active compounds.
Materials and Methods. General scientific method of analysis and synthesis of English-language scientific articles published during the last decade using databases ‘PubMed’, ‘Google Scholar’, ‘Elsevier’, ‘ResearchGate’; methods of systematization, generalization and comparative analysis of databases of computer programs, software packages and data for in silico research; the abstract-logical method was used in the formation of conclusions.
Results and Discussion. The article considers the use of computer programs, software packages and databases for conducting in silico research - methods of research using a computer or computer simulation, for the application of which it is advisable to take into account the molecular mechanisms of the disease, the search and analysis of biological targets for the proposed ligands, calculation of pharmacokinetic parameters, identification of sites of ligands’ metabolism, modeling of intermolecular interaction in order to determine the best ligand-target affinity, which generally leads to a reduction of time, financial and human costs during the search for biologically active compounds. Thanks to molecular docking, it is possible to predict the effectiveness of the ligand-target interaction at the molecular level, and other methods of in silico research allow us to outline structure-activity relationships (SAR, QSAR analysis). Recent advances in chemoinformatics have allowed researchers to use freely available computer programs, software packages, and databases to model the types of intermolecular interactions, calculate binding energy, surface area of a molecule, values of hydrophilicity, lipophilicity, drug-likeness, etc.
Conclusion. In silico research is a real tool for searching new chemical compounds as biologically active compounds, predicting polypharmacology and side effects for approved drugs, studying undesirable pharmacokinetics and toxicity, for the effective use of which it is advisable to use certain algorithms consisting of the following steps: 1) Disease selection and identification of target of biologically active compounds (target identification and validation); 2) Study of the type and structure of active substances in pharmaceuticals and screening analysis of compounds to identify new compounds (Hit discovery) through high-throughput screening (HTS) or in silico methods, in particular virtual screening (VS); 3) Modeling of ligands taking into account ADME/Tox properties (Lead optimisation); 4) Selection of the target receptor, its preparation for in silico research, selection of the binding site of the ligand to the receptor; 5) Search in databases of chemical compounds, drugs, their modification or virtual modeling of the ligand taking into account drug similarity descriptors; 6) Analysis the results of ligand-receptor interaction, visualization of the results of molecular docking.
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