Geng Qi, Zhao Pengcheng, Cao Zhiwen, Wu Zhenyi, Shi Changqi, Zhang Lulu, Yan Lan, Zhang Xiaomeng, Lu Peipei, Shi Jianyu, Lu Cheng
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, People's Republic of China.
School of Life Science, Northwestern Polytechnical University, Xi'an, 710072, China.
Mol Divers. 2025 May 3. doi: 10.1007/s11030-025-11177-8.
The diverse chemical components of traditional Chinese medicine (TCM) exhibit significant therapeutic potential; however, the action mechanisms of these compounds often remain unclear. The use of drug-target prediction can aid in identifying the specific targets of TCM, thereby revealing their bioactivity and mechanisms. The efficiency, cost-effectiveness, and powerful predictive capabilities of artificial intelligence algorithms have led to their emergence as effective tools for accelerating drug-target interaction analysis. To systematically investigate TCM interaction mechanisms, we integrated cosine‑correlation and similarity‑comparison of local network (CSLN) and molecular dynamics (MD) simulations. The CSLN algorithm predicts that 11-beta-hydroxysteroid dehydrogenase-1 (HSD11B1) serves as a common target for the synergistic effects of triptolide (TP) and glycyrrhizic acid (GA). MD simulations indicate that both TP and GA can maintain stable interactions with HSD11B1 and form a common binding hot region. Surface plasmon resonance (SPR) experiments reveal that both TP and GA can effectively bind to HSD11B1, with binding constants of 29.21 μM and 31.75 μM, respectively. When used in combination, the binding constant is 5.74 μM. The combination of CSLN and MD simulations represents an effective tool for the initial analysis and simulation of interaction patterns between TCM and their targets at the computational level. These findings enhance our understanding of the interaction mechanisms between drugs.
中药(TCM)的多种化学成分具有显著的治疗潜力;然而,这些化合物的作用机制往往仍不明确。药物靶点预测的应用有助于确定中药的特定靶点,从而揭示其生物活性和作用机制。人工智能算法的高效性、成本效益和强大的预测能力使其成为加速药物-靶点相互作用分析的有效工具。为了系统地研究中药的相互作用机制,我们整合了局部网络的余弦相关性和相似性比较(CSLN)以及分子动力学(MD)模拟。CSLN算法预测11-β-羟基类固醇脱氢酶-1(HSD11B1)是雷公藤甲素(TP)和甘草酸(GA)协同作用的共同靶点。MD模拟表明,TP和GA都能与HSD11B1保持稳定的相互作用,并形成一个共同的结合热点区域。表面等离子体共振(SPR)实验表明,TP和GA都能有效结合HSD11B1,结合常数分别为29.21 μM和31.75 μM。联合使用时,结合常数为5.74 μM。CSLN和MD模拟的结合是在计算层面初步分析和模拟中药与其靶点之间相互作用模式的有效工具。这些发现加深了我们对药物之间相互作用机制的理解。