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

Zhi-Dong Chen; Lu Zhao; Hsin-Yi Chen; Jia-Ning Gong; Xu Chen; Calvin Yu-Chian Chen

doi:10.1039/d0ra04028b

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

RSC Adv. 2020 Jun 16;10(39):22939-22958. doi: 10.1039/d0ra04028b.

Authors

Zhi-Dong Chen^{1

2}, Lu Zhao^{1

3}, Hsin-Yi Chen¹, Jia-Ning Gong^{1

2}, Xu Chen^{1

2}, Calvin Yu-Chian Chen^{1

4

5}

Affiliations

¹ Artificial Intelligence Medical Center, School of Intelligent Systems Engineering, Sun Yat-sen University Shenzhen 510275 China chenyuchian@mail.sysu.edu.cn.
² School of Pharmaceutical Sciences, Sun Yat-sen University Shenzhen 510275 China.
³ Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou 510655 China.
⁴ Department of Medical Research, China Medical University Hospital Taichung 40447 Taiwan.
⁵ Department of Bioinformatics and Medical Engineering, Asia University Taichung 41354 Taiwan.

Abstract

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 (pIC₅₀). 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.