Department of Urology, Faculty of Medicine, Cukurova University, Adana, Turkey.
Eur Rev Med Pharmacol Sci. 2024 Oct;28(20):4420-4430. doi: 10.26355/eurrev_202410_36865.
Molecular docking studies were conducted to assess the binding affinities of five potential inhibitor candidates [PDB (Protein Data Bank) ID: 6L6E] against Phosphodiesterase 5 (PDE5), with Sildenafil used as the reference compound. The aim of this study is to reveal the potential inhibitory role of plant-derived compounds compared to Sildenafil, a PDE5 inhibitor.
Autodock Vina v. 1.2.5 software was used to dock the protein and each ligand individually. Molecular dynamics simulations assessed the binding affinity of two compounds to the Phosphodiesterase 5A1 (PDE5 A1) enzyme and were carried out using GROMACS 2022.2 RESULTS: Boesenbergin A exhibited the highest affinity at -8.8 kcal/mol, followed by Ginkolide B at -8.5 kcal/mol, Sildenafil at -8.1 kcal/mol, Montanol at -7.8 kcal/mol, Beta-sitosterol at -7.1 kcal/mol, and Eugenol acetate at -6.9 kcal/mol, ranked in descending order. As a result of molecular docking studies, molecular dynamic simulations were performed for Boesenbergin A, which has the highest affinity, and Sildenafil, which is the standard molecule.
Among the two ligands tested, Boesenbergin A exhibited superior binding affinity, surpassing even the standard molecule, Sildenafil. This suggests their potential for modulating enzyme activity and potential relevance in erectile dysfunction treatment.
通过分子对接研究，评估五种潜在抑制剂候选物（PDB（蛋白质数据库）ID：6L6E）与磷酸二酯酶 5（PDE5）的结合亲和力，以西地那非作为参考化合物。本研究旨在揭示与 PDE5 抑制剂西地那非相比，植物衍生化合物的潜在抑制作用。
使用 Autodock Vina v. 1.2.5 软件对蛋白质和每个配体分别进行对接。使用 GROMACS 2022 进行分子动力学模拟，评估两种化合物与磷酸二酯酶 5A1（PDE5 A1）酶的结合亲和力。
Boesenbergin A 表现出最高的亲和力，为-8.8 kcal/mol，其次是 Ginkolide B，为-8.5 kcal/mol，西地那非为-8.1 kcal/mol，Montanol 为-7.8 kcal/mol，β-谷甾醇为-7.1 kcal/mol，乙酸丁香酚为-6.9 kcal/mol，依次递减。分子对接研究的结果表明，对具有最高亲和力的 Boesenbergin A 和标准分子西地那非进行了分子动力学模拟。
在测试的两种配体中，Boesenbergin A 表现出优越的结合亲和力，甚至超过了标准分子西地那非。这表明它们具有调节酶活性的潜力，可能在治疗勃起功能障碍方面具有相关性。
