分子动力学模拟三氯生对烯脂酰-ACP还原酶作用机制研究

Molecular dynamics simulation studies on the mechanism of triclosan binding with FabI

本文利用分子动力学模拟分别研究了蛋白sa Fab I体系、sa Fab I-NADP+体系和sa Fab I-NADP+-TCL体系的稳定性、各氨基酸残基随模拟时间的波动情况以及活性位点处关键氨基酸残基构象的变化规律.研究表明,辅酶NADP+及抑制剂三氯生均可在不同程度上促使蛋白构象稳定.辅酶NADP+可以促使活性位点Loop区残基Y147-Y157残基构象变为规则的卷曲构象;抑制剂三氯生可以促使蛋白与底物结合位点Loop I区残基I94-E108和Loop II区残基R194-F204及活性位点Loop区残基Y147-Y157残基构象变为规则的卷曲构象,构象趋于稳定.上述研究发现对认识三氯生作为抗菌药物机制及相关药物设计具有重要指导意义.

The impact of stability of all complexex, the volatility of each amino acid residues and the comformation of the active site loop of SaFabI, saFabI-NADP~ binary system and saFabI-NADP＋-TCL ternary complex with simulation time were studied by molecular dynamics simulation. The study showed that the NADP＋ and the inhibitor three could promote the stability of conformation of the protein in different degrees. The NADP＋ could promote the stability of conformation of the active site loop Y147 Y157. And the NADP＋ and TCL could promote the stability of the substrate-binding loopI I94 El08 and loopII R194- F204 and the active site loop Y147-Y157. These results aid our understanding of potent inhibitory activity of triclosan and related compounds.