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Studies on Mechanism of Bioactivity and Selectivity of 1,3,4-ThiadiazolInhibitors to AChE/BChE by Molecular Dynamic(PDF)

《南京师大学报（自然科学版）》[ISSN:1001-4616/CN:32-1239/N]

Issue:
2018年01期
Page:
55-
Research Field:
·化学·
Publishing date:

Info

Title:
Studies on Mechanism of Bioactivity and Selectivity of 1,3,4-ThiadiazolInhibitors to AChE/BChE by Molecular Dynamic
Author(s):
Zhao Tengteng; Yang Xueyu; Wang Yali; Zhu Xiaolei
State Key Laboratory of Materials-Oriented Chemical Engineering,College of Chemical Engineering,Nanjing Tech University,Nanjing 210009,China
Keywords:
cholinesterase; 1; 3; 4-thiadiazol inhibitors; molecular dynamics simulation; MM-PBSA method; selectivity
PACS:
O643.1
DOI:
10.3969/j.issn.1001-4616.2018.01.011
Abstract:
Acetylcholinesterase(AChE)and butyrylcholinesterase(BChE)both belonging to the family of cholinesterases(ChEs),which differ in their catalytic properties and inhibition patterns,are highly homologous proteins and play important roles in the cholinergic nervous system. Revealing selectivity mechanism of inhibitors to cholinesterases is an important issue to develop potential Alzheimer’s drugs. In current work,we investigate the bioactivity and selectivity of three 1,3,4-thiadiazol inhibitors to AChE/BChE. The binding interactions between the three inhibitors and AChE/BChE are examined based on the MM-PBSA method. The results demonstrate that three kinds of inhibitors show higher activity to AChE than BChE,and illustrate that the three inhibitors can inhibit AChE selectively. The rank of calculated binding free energies is in good agreement with experimental inhibiting constants of the three inhibitors.

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Last Update: 2018-03-31