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Octopus: a platform for the virtual high-throughput screening of a pool of compounds against a set of molecular targets

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Abstract

Octopus is an automated workflow management tool that is scalable for virtual high-throughput screening (vHTS). It integrates MOPAC2016, MGLTools, PyMOL, and AutoDock Vina. In contrast to other platforms, Octopus can perform docking simulations of an unlimited number of compounds into a set of molecular targets. After generating the ligands in a drawing package in the Protein Data Bank (PDB) format, Octopus can carry out geometry refinement using the semi-empirical method PM7 implemented in MOPAC2016. Docking simulations can be performed using AutoDock Vina and can utilize the Our Own Molecular Targets (OOMT) databank. Finally, the proposed software compiles the best binding energies into a standard table. Here, we describe two successful case studies that were verified by biological assay. In the first case study, the vHTS process was carried out for 22 (phenylamino)urea derivatives. The vHTS process identified a metalloprotease with the PDB code 1GKC as a molecular target for derivative LE&007. In a biological assay, compound LE&007 was found to inhibit 80% of the activity of this enzyme. In the second case study, compound Tx001 was submitted to the Octopus routine, and the results suggested that Plasmodium falciparum ATP6 (PfATP6) as a molecular target for this compound. Following an antimalarial assay, Tx001 was found to have an inhibitory concentration (IC50) of 8.2 μM against PfATP6. These successful examples illustrate the utility of this software for finding appropriate molecular targets for compounds. Hits can then be identified and optimized as new antineoplastic and antimalarial drugs. Finally, Octopus has a friendly Linux-based user interface, and is available at www.drugdiscovery.com.br.

Octopus: A platform for inverse virtual screening (IVS) to search new molecular targets for drugs.

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Acknowledgements

The authors are grateful for the support provided by the Foundation for Research Support of Minas Gerais (FAPEMIG APQ-00557-14 and APQ-02860-16), the Higher Level Personnel Improvement Commission (CAPES), the National Research Council (CNPq UNIVERSAL 449984/2014-1), and Graduated Programs in Pharmaceutical Sciences (PPGCS) and Biotechnology (PPGBiotec) from the Federal University of Sao Joao del Rei (UFSJ) and the Federal Center for Technological Education of Minas Gerais (CEFET-MG). A.G. Taranto is grateful to Mr. Pedro for the “Ignorância Zero” initiative.

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Authors and Affiliations

  1. Universidade Federal de São João del Rei—Campus Centro-Oeste, Divinópolis, MG, Brazil

    Eduardo Habib Bechelane Maia, Vinícius Alves Campos, Bianca dos Reis Santos, Marina Santos Costa, Iann Gabriel Lima, Rosy I. M. A. Ribeiro & Alex Gutterres Taranto

  2. Centro Federal de Educação Tecnológica de Minas Gerais—Campus Divinópolis, Divinópolis, MG, Brazil

    Eduardo Habib Bechelane Maia, Vinícius Alves Campos, Bianca dos Reis Santos, Marina Santos Costa & Iann Gabriel Lima

  3. Universidade Federal do Espírito Santo—UFES, Vitória, ES, Brazil

    Sandro J. Greco, Felipe M. Munayer & Alisson Marques da Silva

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  1. Eduardo Habib Bechelane Maia
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  2. Vinícius Alves Campos
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Correspondence to Alex Gutterres Taranto.

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This paper belongs to Topical Collection Brazilian Symposium of Theoretical Chemistry (SBQT 2015)

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Maia, E.H.B., Campos, V.A., dos Reis Santos, B. et al. Octopus: a platform for the virtual high-throughput screening of a pool of compounds against a set of molecular targets. J Mol Model 23, 26 (2017). https://doi.org/10.1007/s00894-016-3184-9

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