A novel artificial intelligence protocol to investigate potential leads for Parkinson's disease

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(50)). 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.