Chen Zhi-Dong, Zhao Lu, Chen Hsin-Yi, Gong Jia-Ning, Chen Xu, Chen Calvin Yu-Chian
Artificial Intelligence Medical Center, School of Intelligent Systems Engineering, Sun Yat-sen University Shenzhen 510275 China
School of Pharmaceutical Sciences, Sun Yat-sen University Shenzhen 510275 China.
RSC Adv. 2020 Jun 16;10(39):22939-22958. doi: 10.1039/d0ra04028b.
Previous studies have shown that small molecule inhibitors of NLRP3 may be a potential treatment for Parkinson's disease (PD). NACHT, LRR and PYD domains-containing protein 3 (NLRP3), heat shock protein HSP 90-beta (HSP90AB1), caspase-1 (CASP1) and cellular tumor antigen p53 (TP53) have significant involvement in the pathogenesis pathway of PD. Molecular docking was used to screen the traditional Chinese medicine database TCM Database@Taiwan. Top traditional Chinese medicine (TCM) compounds with high affinities based on Dock Score were selected to form the drug-target interaction network to investigate potential candidates targeting NLRP3, HSP90AB1, CASP1, and TP53 proteins. Artificial intelligence model, 3D-Quantitative Structure-Activity Relationship (3D-QSAR) were constructed respectively utilizing training sets of inhibitors against the four proteins with known inhibitory activities (pIC). The results showed that 2007_22057 (an indole derivative), 2007_22325 (a valine anhydride) and 2007_15317 (an indole derivative) might be a potential medicine formula for the treatment of PD. Then there are three candidate compounds identified by the result of molecular dynamics.
先前的研究表明，NLRP3的小分子抑制剂可能是治疗帕金森病（PD）的一种潜在疗法。含NACHT、LRR和PYD结构域的蛋白3（NLRP3）、热休克蛋白HSP 90-β（HSP90AB1）、半胱天冬酶-1（CASP1）和细胞肿瘤抗原p53（TP53）在PD的发病机制途径中具有重要作用。利用分子对接技术筛选了台湾中医药数据库。根据对接分数选择具有高亲和力的顶级中药化合物，构建药物-靶点相互作用网络，以研究靶向NLRP3、HSP90AB1、CASP1和TP53蛋白的潜在候选物。分别利用针对四种具有已知抑制活性（pIC）的蛋白质的抑制剂训练集构建人工智能模型、三维定量构效关系（3D-QSAR）。结果表明，2007_22057（一种吲哚衍生物）、2007_22325（一种缬氨酸酐）和2007_15317（一种吲哚衍生物）可能是治疗PD的潜在药物配方。然后通过分子动力学结果鉴定出三种候选化合物。
