Structure-based multi-ligand molecular modeling to predict the synergistic effects of limonin and obacunone from Simiao pill against nitric oxide synthase 3 associated with hyperuricemia  

作　　者：Qing-Hong Chen Xiao-Mei Chen Xiao-Hu Chen Yan-Ting You Shu-Xuan Yang Chuang-Hai Wu Mei-Lin Chen Ming-Di Li Akari Komori Yan-Yan Liu Andrew Hung Xiao-Shan Zhao Hong Li 

机构地区：[1]Department of Traditional Chinese Medicine,Zhujiang Hospital,Southern Medical University,Guangzhou 510280,China [2]School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515,China [3]Centre of General Practice,The Seventh Affiliated Hospital,Southern Medical University,Foshan 528244,China [4]Department of Preventive Health Care,Qingdao Hiser Hospital Affiliated to Qingdao University(Qingdao Traditional Chinese Medicine Hospital),Qingdao 266033,China [5]School of Science,STEM College,RMIT University,Melbourne,Victoria 3000,Australia

出　　处：《Precision Medicine Research》2023年第3期11-15,共5页精准医学研究

基　　金：This work was funded by the Key Project of National Natural Science Foundation of China[grant number 81830117];Joint Funds of National Natural Science Foundation of China[grant number U22A20365];National Natural Science Foundation of China[grant numbers 8220140209,82274499];Guangdong Basic and Applied Basic Research Foundation[grant number 2021A1515110082];China Postdoctoral Science Foundation[grant number 2022M711534];Science&Technical Plan of Guangzhou,Guangdong,China[grant number 201903010069].

摘　　要：Hyperuricemia(HUA)mainly occurs because of purine metabolism disorders.We recently proposed that limonin from Simiao pill may have therapeutic effects on nitric oxide synthase 3(NOS3)that is related to HUA.Concurrently,our previous work employed a new method,structure-based multi-ligand molecular modeling,to identify potential agents from a herbal formula that may produce synergistic effects and may have the potential to develop combination drugs.Therefore,we employed multi-ligand modeling to seek compounds with potential synergistic effects with limonin against NOS3.We obtained 403 multi-ligand docking results between 403 compounds and the limonin-NOS3 complex(average affinity–8.297 kcal/mol).Then we selected the top 10 highest binding affinity compounds for virtual pharmacokinetic and toxicity screening and we found that only obacunone passed all filters.We further subjected obacunone,bound to limonin and NOS3,to molecular dynamics simulations.We found that the NOS3-limonin-obacunone complex was more stable than the NOS3-limonin complex,based on the root mean square deviation of backbone Cαatoms and root mean square fluctuation,which suggests that synergistic effects may exist between limonin and obacunone.Further cell and animal experimental research is required to verify our results.

关 键 词：HYPERURICEMIA synergistic mechanism Chinese herbal medicine complementary and alternative medicine molecular docking molecular dynamics simulations in silico analysis 

分 类 号：O62[理学—有机化学]