地黄梓醇和乙酰胆碱酯酶作用的分子动力学模拟

Molecular dynamics simulationon the interactions between rehmannia catalpol and acetylcholinesterase

梓醇能有效的的改善阿茨海默尔症状,但与乙酰胆碱酯酶(Acetylcholinesterase,AchE)作用的分子机制尚不明晰.本文运用分子动力学模拟、结合自由能的计算和丙氨酸突变扫描的方法研究了两者的结合模式,结果表明:梓醇结合位点为乙酰胆碱酯酶的催化活性中心,并形成3个氢键,结合自由能为-60.59 k J/mol,结合的主要驱动力是范德华力和静电作用力,主要抑制力是极性溶剂化能,Tyr151和Gln176是两者结合的关键氨基酸.这些研究为开发高效的Ach E梓醇类似物抑制剂提供理论支持.

Catalpol could effectively improve the symptom of Alzheimer’s disease,but the interaction mechanism with acetylcholinesterase(AchE) is not clearly. In this study,the binding mode between catalpol and AchE was investigated using molecular dynamics simulation,the binding free energy calculation and alanine scanning mutagenesis experiment methods. The results showed that the binding site of catalpol locate in the region of AchE catalytic active site,The binding complex forms three hydrogen bonds with the binding free energy-60. 59 k J/mol,The van der Wals and electrostatic are the main driving forces,The polar solvation energy is the main resistance force and Tyr151 and Gln176 are the key amino acids of the combination. These date could provide the theoretical fundamental for further exploitations of efficient AchE inhibitors of catalpol analogues.