Chunying Du, Hua Yin, Aowei Xie, Junhong Yu, Yifan Wang, Fengli Yao, Siyu Zhang, Yidan Zhang, Lu Liu, Peng Wang, Jianjun Dong, Ximing Xu
Hyperuricemia is mainly caused by insufficient renal urate excretion. Urate transporter 1 (URAT1), an organic anion transporter, is the main protein responsible for urate reabsorption. In this study, we utilized artificial intelligence-based AlphaFold2 program to construct URAT1 structural model. After molecular docking and conformational evaluation, four e-pharmacophoric models were constructed based on the complex structures of probenecid-URAT1, benzbromarone-URAT1, lesinurad-URAT1, and verinurad-URAT1. Combining pharmacophore modeling, molecular docking, MM/GBSA calculation and ADME prediction, 25 flavonoids were selected from the natural products database containing 10,968 molecules...
March 29, 2024: Journal of Biomolecular Structure & Dynamics