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| Interaction Mechanism Between AChE and 1, 7-Diazacarbazole Inhibitors Based on Molecular Dynamics Simulations |
| Author Name | Affiliation | E-mail | | ZHAO Teng-Teng | State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing 210009, China | | | YANG Xue-Yu | State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing 210009, China | | | DONG Ke-Ke | State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing 210009, China | | | ZHU Xiao-Lei | State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing 210009, China | xlzhu@njtech.edu.cn |
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| Abstract: The molecular docking, molecular dynamics (MD) simulation, and binding free energy analysis are used to gain the insight into the binding mechanism of three 1,7-diazacarbazole derivatives (marked as M1, M2, and M3, respectively) with AChE at the atom level. The electrostatic and van der Waals (vdW) interactions of the three inhibitors with AChE are analyzed and discussed. The ranking of the computed binding free energies based on MM-PBSA method is consistent with the ranking of experimental bioactivities for the three inhibitors. The hydrogen-bond interactions of the inhibitors with S286 are favorable to the binding affinity of inhibitors to AChE. The van der Waals interactions, especially the key contacts with W279 and Y334 have larger contributions to the binding free energy and play an important role in distinguishing the bioactivities of M1(or M2) and M3. |
| Keywords: Alzheimer's disease AChE 1,7-diazacarbazole inhibitor molecular dynamics simulation MM-PBSA |
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| ZHAO Teng-Teng,YANG Xue-Yu,DONG Ke-Ke,ZHU Xiao-Lei.Interaction Mechanism Between AChE and 1, 7-Diazacarbazole Inhibitors Based on Molecular Dynamics Simulations[J].Chinese Journal of Inorganic Chemistry,2017,33(11):2065-2074. |
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