Olivero-Acosta Maria, Maldonado-Rojas Wilson, Olivero-Verbel Jesus
Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, Zaragocilla Campus, University of Cartagena, Cartagena 130015, Colombia.
Molecules. 2017 Feb 17;22(2):308. doi: 10.3390/molecules22020308.
Small molecules found in natural products provide therapeutic benefits due to their pharmacological or biological activity, which may increase or decrease the expression of human epidermal growth factor receptor (HER), a promising target in the modification of signaling cascades involved in excessive cellular growth. In this study, in silico molecular protein-ligand docking protocols were performed with AutoDock Vina in order to evaluate the interaction of 800 natural compounds (NPs) from the NatProd Collection (http://www.msdiscovery.com/natprod.html), with four human HER family members: HER1 (PDB: 2ITW), HER2 (PDB: 3PP0), HER3 (PDB: 3LMG) and HER4 (PDB: 2R4B). The best binding affinity values (kcal/mol) for docking pairs were obtained for HER1-podototarin (-10.7), HER2-hecogenin acetate (-11.2), HER3-hesperidin (-11.5) and HER4-theaflavin (-10.7). The reliability of the theoretical calculations was evaluated employing published data on HER inhibition correlated with in silico binding calculations. IC values followed a significant linear relationship with the theoretical binding Affinity data for HER1 ( = 0.656, < 0.0001) and HER2 ( = 0.543, < 0.0001), but not for HER4 ( = 0.364, > 0.05). In short, this methodology allowed the identification of several NPs as HER inhibitors, being useful in the discovery and design of more potent and selective anticancer drugs.
天然产物中发现的小分子因其药理或生物活性而具有治疗作用，这些活性可能会增加或降低人类表皮生长因子受体（HER）的表达，HER是参与过度细胞生长的信号级联修饰中的一个有前景的靶点。在本研究中，使用AutoDock Vina进行了计算机模拟分子蛋白-配体对接实验，以评估来自NatProd Collection（http://www.msdiscovery.com/natprod.html）的800种天然化合物（NP）与四种人类HER家族成员的相互作用：HER1（PDB：2ITW）、HER2（PDB：3PP0）、HER3（PDB：3LMG）和HER4（PDB：2R4B）。对接对的最佳结合亲和力值（kcal/mol）分别为HER1-波多托他林（-10.7）、HER2-乙酸海柯皂苷元（-11.2）、HER3-橙皮苷（-11.5）和HER4-茶黄素（-10.7）。利用已发表的与计算机模拟结合计算相关的HER抑制数据评估了理论计算的可靠性。IC值与HER1（r = 0.656，p < 0.0001）和HER2（r = 0.543，p < 0.0001）的理论结合亲和力数据呈显著线性关系，但与HER4（r = 0.364，p > 0.05）无关。简而言之，该方法能够鉴定出几种作为HER抑制剂的NP，有助于发现和设计更有效、更具选择性的抗癌药物。
