Computational Investigation into the Interactions of Traditional Chinese Medicine Molecules of WenQingYin with GluR2.

Yu-Hui Tseng,Yu-Ren Huang,Cheng-Lung Chen,Po-Hsiang Chuang

doi:10.3390/ijms18071443

Abstract

Docking and molecular dynamics simulations have been carried out to investigate the interaction of a traditional Chinese medicine, WenQingYin, with the glutamate receptor 2 (GluR2) subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. Four representative drug components of WenQingYin, namely 2-(3,4-dihydroxyphenyl)-5,6,7-trihydroxy-4H-chromen-4-one (PHF), 4-hydroxy-3-methoxybenzoic acid (HMB), 4-(2,3-dihydroxy-3-methylbutoxy)-7H-furo[3,2-g]chromen-7-one (DHMBP) and methyl 7-formylcyclopenta[c]pyran-4-carboxylate (cerbinal), and their complexes with GluR2 were simulated. Our results show that PHF, HMB, and DHMBP formed a partial hydrogen bond with GluR2 in its ligand-binding domain. However, cerbinal was not stable in the ligand-binding domain of GluR2 and induced a significant change in the structure of GluR2. Three-dimensional plots represent the contact and movement situation of the traditional Chinese medicine molecules in the ligand-binding domain. The combined results of the docking and molecular dynamics simulations provide insight into the interaction between these traditional Chinese medicine molecules and proteins.

Highlights

Traditional Chinese medicine (TCM) plays an important role in Asia, with an increasing number of TCMs being used to treat diseases, such as influenza [1], diabetes [2,3], cancer [4,5,6,7], and neurological disorders [8,9]
We investigated the effects of four traditional Chinese medicine molecules (PHF, hydroxy-3-methoxybenzoic acid (HMB), DHMBP and cerbinal), which are the main compounds in WenQingYin, upon the amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor by using molecular dynamics (MD) simulations
PHF, HMB and DHMBP formed partial hydrogen bonds with glutamate receptor 2 (GluR2) in the ligand-binding domain, which led to the formation of more stable drug–protein complexes, and these molecules are antagonists for GluR2

Summary

Introduction

Traditional Chinese medicine (TCM) plays an important role in Asia, with an increasing number of TCMs being used to treat diseases, such as influenza [1], diabetes [2,3], cancer [4,5,6,7], and neurological disorders [8,9]. Hung et al investigated the inhibitory effect of a series of TCMs on human histone deacetylase 2, which is implicated in Alzheimer’s disease [9]. These studies show that TCM have beneficial effects in neurological disorders. The structure of the AMPA subunit GluR2, when bound to a wide variety of agonists, partial agonists, and antagonists, has provided compelling clues for the structural basis of channel activation and desensitization [16]

Methods

Results

Conclusion