蛋白质 Bcl-2 以其抗凋亡特性而闻名，与癌症发病机制有关。鉴定负责促进改善细胞存活和发育的主要基因为预防恶性肿瘤进展中的细胞死亡提供了令人信服的证据。大量研究提供的证据表明，恶性细胞中 Bcl-2 的丰度较高，这表明抑制 Bcl-2 表达可能是癌症治疗的一种可行的治疗方法。在这项研究中，我们使用包含传统中药 (TCM) 成分的数据库获取了化合物集合。最初，我们建立了药效团模型，并利用它在中药数据库中搜索潜在的化合物。选择适合度得分超过 0.75 的化合物进行进一步分析。吸收、分布、代谢、排泄和毒性 (ADMET) 分析确定了六种具有良好治疗特性的化合物。成功通过基于药效模型的初步筛选过程的化合物将接受进一步的评估。采用超精密 (XP) 对接来识别具有最有利 XP 对接分数的化合物。使用分子力学广义玻恩表面积 (MM-GBSA) 方法进行进一步分析，计算总自由结合能。通过姜黄素和表没食子儿茶素没食子酸酯 (EGCG) 的 100 ns 分子动力学模拟评估预期配体分子与靶蛋白 Bcl-2 之间的结合能。这项研究的结果证明了一种分子结构的鉴定，当 Bcl-2 与配体 EGCG 结合时，该结构可有效抑制 Bcl-2 的功能。因此，这一发现为开发能够有效解决炎症和肿瘤疾病的药物提供了一条新途径。© 2024。作者。

The protein Bcl-2, well-known for its anti-apoptotic properties, has been implicated in cancer pathogenesis. Identifying the primary gene responsible for promoting improved cell survival and development has provided compelling evidence for preventing cellular death in the progression of malignancies. Numerous research studies have provided evidence that the abundance of Bcl-2 is higher in malignant cells, suggesting that suppressing Bcl-2 expression could be a viable therapeutic approach for cancer treatment. In this study, we acquired a compound collection using a database that includes constituents from Traditional Chinese Medicine (TCM). Initially, we established a pharmacophore model and utilized it to search the TCM database for potential compounds. Compounds with a fitness score exceeding 0.75 were selected for further analysis. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis identified six compounds with favorable therapeutic characteristics. The compounds that successfully passed the initial screening process based on the pharmacodynamic model were subjected to further evaluation. Extra-precision (XP) docking was employed to identify the compounds with the most favorable XP docking scores. Further analysis using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method to calculate the overall free binding energy. The binding energy between the prospective ligand molecule and the target protein Bcl-2 was assessed by a 100 ns molecular dynamics simulation for curcumin and Epigallocatechin gallate (EGCG). The findings of this investigation demonstrate the identification of a molecular structure that effectively inhibits the functionality of the Bcl-2 when bound to the ligand EGCG. Consequently, this finding presents a novel avenue for the development of pharmaceuticals capable of effectively addressing both inflammatory and tumorous conditions.© 2024. The Author(s).