Department of PG Studies in Biotechnology, Nrupathunga University, Nrupathunga Road, Bangalore 560001, India.
Department of Clinical Nutrition, College of Applied Health Sciences in Ar Rass, Qassim University, Al Qassim Region, Ar Rass 51921, Saudi Arabia.
Molecules. 2023 Feb 7;28(4):1588. doi: 10.3390/molecules28041588.
In the present study, the binding affinity of 52 bioactive secondary metabolites from towards the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein (PDB: 2W3L) structure was identified by using in silico molecular docking and molecular dynamics simulation. The molecular docking results demonstrated that the binding energies of docked compounds with Bcl-2 protein ranged from -5.3 kcal/mol to -10.1 kcal/mol. However, the lowest binding energy (-10.1 kcal/mol) was offered by Friedelin against Bcl-2 protein when compared to other metabolites and the standard drug Obatoclax (-8.4 kcal/mol). The molecular dynamics simulations revealed that the Friedelin-Bcl-2 protein complex was found to be stable throughout the simulation period of 100 ns. Overall, the predicted Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of Friedelin are relatively better than Obatoclax, with the most noticeable differences in many parameters where Friedelin has no AMES toxicity, hepatotoxicity, and skin sensitization. The ADMET profiling of selected compounds supported their in silico drug-likeness properties. Based on the computational analyses, the present study concluded that Friedelin of was found to be the potential inhibitor of the Bcl-2 protein, which merits attention for further in vitro and in vivo studies before clinical trials.
在本研究中，通过计算机分子对接和分子动力学模拟，鉴定了 52 种生物活性次生代谢物与抗凋亡 B 细胞淋巴瘤-2（Bcl-2）蛋白（PDB：2W3L）结构的结合亲和力。分子对接结果表明，对接化合物与 Bcl-2 蛋白的结合能范围为-5.3 kcal/mol 至-10.1 kcal/mol。然而，与其他代谢物和标准药物 Obatoclax（-8.4 kcal/mol）相比，Friedelin 对 Bcl-2 蛋白的结合能最低（-10.1 kcal/mol）。分子动力学模拟表明，Friedelin-Bcl-2 蛋白复合物在 100 ns 的模拟时间内被发现是稳定的。总体而言，Friedelin 的预测吸收、分布、代谢、排泄和毒性（ADMET）特性相对优于 Obatoclax，在许多参数上的差异最为明显，其中 Friedelin 没有 AMES 毒性、肝毒性和皮肤致敏性。所选化合物的 ADMET 分析支持它们的计算机药物相似性特性。基于计算分析，本研究得出结论， 中的 Friedelin 被发现是 Bcl-2 蛋白的潜在抑制剂，值得在临床试验前进行进一步的体外和体内研究。
