Maia Eduardo Habib Bechelane, Campos Vinícius Alves, Dos Reis Santos Bianca, Costa Marina Santos, Lima Iann Gabriel, Greco Sandro J, Ribeiro Rosy I M A, Munayer Felipe M, da Silva Alisson Marques, Taranto Alex Gutterres
Universidade Federal de São João del Rei-Campus Centro-Oeste, Divinópolis, MG, Brazil.
Centro Federal de Educação Tecnológica de Minas Gerais-Campus Divinópolis, Divinópolis, MG, Brazil.
J Mol Model. 2017 Jan;23(1):26. doi: 10.1007/s00894-016-3184-9. Epub 2017 Jan 7.
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 (IC) 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 . Graphical Abstract Octopus: A platform for inverse virtual screening (IVS) to search new molecular targets for drugs.
章鱼（Octopus）是一种自动化工作流程管理工具，可扩展用于虚拟高通量筛选（vHTS）。它集成了MOPAC2016、MGLTools、PyMOL和AutoDock Vina。与其他平台不同，章鱼可以对无限数量的化合物进行对接模拟，使其作用于一组分子靶点。在以蛋白质数据库（PDB）格式的绘图软件包中生成配体后，章鱼可以使用MOPAC2016中实现的半经验方法PM7进行几何结构优化。对接模拟可以使用AutoDock Vina进行，并可以利用我们自己的分子靶点（OOMT）数据库。最后，该软件将最佳结合能编译成标准表格。在此，我们描述了两个经生物学测定验证的成功案例研究。在第一个案例研究中，对22种（苯氨基）脲衍生物进行了vHTS过程。vHTS过程确定了PDB代码为1GKC的金属蛋白酶作为衍生物LE&007的分子靶点。在生物学测定中，发现化合物LE&007可抑制该酶80%的活性。在第二个案例研究中，化合物Tx001被提交给章鱼程序，结果表明恶性疟原虫ATP6（PfATP6）是该化合物的分子靶点。经过抗疟疾测定，发现Tx001对PfATP6的抑制浓度（IC）为8.2 μM。这些成功的例子说明了该软件在为化合物寻找合适分子靶点方面的实用性。然后可以将命中的靶点识别出来并优化为新的抗肿瘤和抗疟疾药物。最后，章鱼有一个基于Linux的友好用户界面，可在www.drugdiscovery.com.br上获取。图形摘要：章鱼：一个用于反向虚拟筛选（IVS）以寻找新的药物分子靶点的平台。
