| Summary: | 博士 === 國立中山大學 === 化學系研究所 === 105 === Molecular docking and molecular dynamics (MD) simulations have been carried out to investigate the interaction of a traditional Chinese medicine (TCM), WenQingYin, with the glutamate receptor 2 (GluR2) and cyclooxygenase-2 (COX-2). Four representative drug components of TCM molecules, 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 and COX-2 were simulated.
In GluR2 systems, 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 TCM molecules in the ligand-binding domain of GluR2. In COX-2 systems, our results show that PHF, DHMBP and cerbinal were stable and formed a partial hydrogen bond with its active site. However, the hydrogen bonds are formed on HMB in docking but not observed in MD simulation. It shows that the HMB have an unstable interaction with COX-2.
The interaction between drugs and proteins is a major factor influencing the drug efficacy. The stability of drugs in the active site affects the activity of the protein. Our results suggest that PHF, HMB and DHMBP are considered to be GluR2 antagonists; PHF, DHMBP and cerbinal are considered to be COX-2 inhibitors. The combined results of the docking and molecular dynamics simulations provide insight into the interaction between these traditional Chinese medicine molecules and proteins.
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