RESUMEN
INTRODUCTION: Molecular docking has been consolidated as one of the most important methods in the molecular modeling field. It has been recognized as a prominent tool in the study of protein-ligand complexes, to describe intermolecular interactions, to accurately predict poses of multiple ligands, to discover novel promising bioactive compounds. Molecular docking methods have evolved in terms of their accuracy and reliability; but there are pending issues to solve for improving the connection between the docking results and the experimental evidence. AREAS COVERED: In this article, the author reviews very recent innovative molecular docking applications with special emphasis on reverse docking, treatment of protein flexibility, the use of experimental data to guide the selection of docking poses, the application of Quantum mechanics(QM) in docking, and covalent docking. EXPERT OPINION: There are several issues being worked on in recent years that will lead to important breakthroughs in molecular docking methods in the near future These developments are related to more efficient exploration of large datasets and receptor conformations, advances in electronic description, and the use of structural information for guiding the selection of results.
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Descubrimiento de Drogas , Proteínas , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Unión Proteica , Proteínas/metabolismo , Reproducibilidad de los ResultadosRESUMEN
Molecular docking is a useful and powerful computational method for the identification of potential interactions between small molecules and pharmacological targets. In reverse docking, the ability of one or a few compounds to bind a large dataset of proteins is evaluated in silico. This strategy is useful for identifying molecular targets of orphan bioactive compounds, proposing new molecular mechanisms, finding alternative indications of drugs, or predicting drug toxicity. Herein, we describe a detailed reverse docking protocol for the identification of potential targets for 4-hydroxycoumarin (4-HC). Our results showed that RAC1 is a target of 4-HC, which partially explains the biological activities of 4-HC on cancer cells. The strategy reported here can be easily applied to other compounds and protein datasets.
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4-Hidroxicumarinas/farmacología , Antineoplásicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales/métodos , Simulación del Acoplamiento Molecular/métodos , 4-Hidroxicumarinas/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Sitios de Unión , Simulación por Computador , Bases de Datos de Proteínas , Humanos , Ligandos , Terapia Molecular Dirigida , Conformación Proteica , Programas Informáticos , Proteína de Unión al GTP rac1/química , Proteína de Unión al GTP rac1/metabolismoRESUMEN
ABSTRACT The discovery of arteannuin (qinghaosu) in the 20th Century was a major advance for medicine. Besides functioning as a malaria therapy, arteannuin is a pharmacological agent in a range of other diseases, but its mechanism of action remains obscure. In this study, the reverse docking server PharmMapper was used to identify potential targets of arteannuin. The results were checked using the chemical-protein interactome servers DRAR-CPI and DDI-CPI, and verified by AutoDock Vina. The results showed that neprilysin (also known as CD10), a common acute lymphoblastic leukaemia antigen, was the top disease-related target of arteannuin. The chemical-protein interactome and docking results agreed with those of PharmMapper, further implicating neprilysin as a potential target. Although experimental verification is required, this study provides guidance for future pharmacological investigations into novel clinical applications for arteannuin.