Radusky Leandro, Ruiz-Carmona Sergio, Modenutti Carlos, Barril Xavier, Turjanski Adrian G, Martí Marcelo A
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , 1053 Buenos Aires, Argentina.
Insituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN-CONICET) , Pabellón II, Buenos Aires C1428EHA, Argentina.
J Chem Inf Model. 2017 Aug 28;57(8):1741-1746. doi: 10.1021/acs.jcim.7b00241. Epub 2017 Jul 27.
Virtual screening is a powerful methodology to search for new small molecule inhibitors against a desired molecular target. Usually, it involves evaluating thousands of compounds (derived from large databases) in order to select a set of potential binders that will be tested in the wet-lab. The number of tested compounds is directly proportional to the cost, and thus, the best possible set of ligands is the one with the highest number of true binders, for the smallest possible compound set size. Therefore, methods that are able to trim down large universal data sets enriching them in potential binders are highly appreciated. Here we present LigQ, a free webserver that is able to (i) determine best structure and ligand binding pocket for a desired protein, (ii) find known binders, as well as potential ligands known to bind to similar protein domains, (iii) most importantly, select a small set of commercial compounds enriched in potential binders, and (iv) prepare them for virtual screening. LigQ was tested with several proteins, showing an impressive capacity to retrieve true ligands from large data sets, achieving enrichment factors of over 10%. LigQ is available at http://ligq.qb.fcen.uba.ar/ .
虚拟筛选是一种强大的方法，用于寻找针对目标分子靶点的新型小分子抑制剂。通常，它涉及评估数千种化合物（来自大型数据库），以便选择一组将在湿实验室中进行测试的潜在结合物。测试化合物的数量与成本直接成正比，因此，对于尽可能小的化合物集规模，最佳的配体集是具有最多真实结合物的配体集。因此，能够缩减大型通用数据集并富集潜在结合物的方法备受青睐。在这里，我们介绍LigQ，一个免费的网络服务器，它能够（i）为目标蛋白质确定最佳结构和配体结合口袋，（ii）找到已知的结合物以及已知与相似蛋白质结构域结合的潜在配体，（iii）最重要的是，选择一小批富含潜在结合物的商业化合物，以及（iv）为虚拟筛选准备这些化合物。LigQ已针对多种蛋白质进行了测试，显示出从大型数据集中检索真实配体的惊人能力，富集因子超过10%。可通过http://ligq.qb.fcen.uba.ar/访问LigQ。
