The shikimate pathway consists of seven enzymatic steps involved in the conversion of erythrose-4-phosphate and phosphoenolpyruvate to chorismate and also responsible to the production of aromatic amino acids, such as phenylalanine, tyrosine, and tryptophan which are essential to the bacterial metabolism. The 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS) and 5-enolpyruvylshikimate 3-phosphate synthase (EPSPS) catalyze important steps in the shikimate pathway using as substrate the phosphoenolpyruvate (PEP). Due to the importance of PEP in shikimate pathway, its structure has been investigated to develop new bioinspired competitive inhibitors against DAHPS and EPSPS. In the present study, we perform a literature survey of 28 PEP derivatives, then we analyzed the selectivity and affinity of these compounds against the EPSPS and DAHPS structures using consensual molecular docking, pharmacophore prediction, molecular dynamics (MD) simulations, and binding free energy calculations. Here, we propose consistent binding modes of the selected ligands and indicate that their structures show interesting pharmacophoric properties related to multi-targets inhibitors for both enzymes. Our computational results are supported by previous experimental findings related to the interactions of PEP derivatives with DAHPS and EPSPS structures.

sh草酸酯途径由七个酶促步骤组成，这些步骤涉及将四磷酸赤藓糖和磷酸烯醇丙酮酸转化为分支酸酯，并且还负责产生芳香氨基酸，例如苯丙氨酸，酪氨酸和色氨酸，这对于细菌的代谢至关重要。3-脱氧-D-阿拉伯-庚酸七磷酸酯合酶（DAHPS）和5-烯丙基丙酮酸shi草酸酯3-磷酸合酶（EPSPS）以磷酸烯醇丙酮酸（PEP）为底物催化the草酸酯途径中的重要步骤。由于PEP在sh草酸途径中的重要性，已经对其结构进行了研究，以开发出新的生物启发性抗DAHPS和EPSPS竞争性抑制剂。在本研究中，我们对28种PEP衍生物进行了文献调查，然后，我们使用共识性分子对接，药效基团预测，分子动力学（MD）模拟和结合自由能计算，分析了这些化合物对EPSPS和DAHPS结构的选择性和亲和力。在这里，我们提出了所选配体的一致结合模式，并表明它们的结构显示出与两种酶的多靶标抑制剂相关的有趣药理学特性。我们的计算结果得到了与PEP衍生物与DAHPS和EPSPS结构相互作用的先前实验结果的支持。我们提出了所选配体的一致结合模式，并表明它们的结构显示出与两种酶的多靶标抑制剂有关的有趣的药理特性。我们的计算结果得到了与PEP衍生物与DAHPS和EPSPS结构相互作用的先前实验结果的支持。我们提出了所选配体的一致结合模式，并表明它们的结构显示出与两种酶的多靶标抑制剂有关的有趣的药理特性。我们的计算结果得到了与PEP衍生物与DAHPS和EPSPS结构相互作用的先前实验结果的支持。