Departamento de Farmacología y Unidad Periférica de Investigación en Biomedicina Traslacional, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico.
Department of Drug Design, Graduate School of Science and Engineering, University of Groningen (RUG), Groningen, The Netherlands.
Methods Mol Biol. 2021;2174:31-43. doi: 10.1007/978-1-0716-0759-6_4.
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.
分子对接是一种有用且强大的计算方法，可用于鉴定小分子和药理学靶标之间的潜在相互作用。在反向对接中，通过计算机评估一种或几种化合物与大量蛋白质结合的能力。这种策略可用于鉴定孤儿生物活性化合物的分子靶标、提出新的分子机制、寻找药物的替代适应症，或预测药物毒性。在此，我们描述了一个详细的反向对接方案，用于鉴定 4-羟基香豆素（4-HC）的潜在靶标。我们的结果表明，RAC1 是 4-HC 的靶标，这部分解释了 4-HC 对癌细胞的生物学活性。这里报道的策略可以很容易地应用于其他化合物和蛋白质数据集。
