结合小分子结合剂和非结合剂的自由能量景观与FMN核转换器:全原子分子动力学
Junichi Higo1,2, Gert-Jan Bekker3, Narutoshi Kamiya1
1Graduate School of Information Science, University of Hyogo, Kobe, Hyogo 650-0047, Japan.
Biophysics and physicobiology
|February 12, 2024
概括
利博西尔B比利博西尔A更强烈地结合了FMN рибо交换机胺,具有不同的结合途径和自由能量景观. 分子动力学模拟揭示了连接体如何在体中导航.
科学领域:
- 分子生物学分子生物学
- 计算化学的计算化学
- 生物物理学的生物物理.
背景情况:
- FMN рибо开关是一种RNA分子,具有绑定小分子的aptamer域.
- 利博西尔A和B是光学异构体,它们与FMN рибо交换机aptamer的深袋结合.
- 了解配体-RNA相互作用对于药物发现和分子生物学至关重要.
研究的目的:
- 为了研究 ribocil A 和 B 与 FMN рибо交换机合体的结合机制.
- 使用计算方法比较这些光学异构体的结合亲和和路径.
- 阐明特定相互作用和能量场景在联体-吸收体结合中的作用.
主要方法:
- 用通用整体模拟方法 (mD-VcMD) 研究结合过程.
- 模拟在明确溶剂中进行,从分离联结体和aptamer开始.
- 计算和分析了自由能量景观和结合途径.
主要成果:
- 根据实验数据,Aptamer-ribocil B的结合被发现比Aptamer-ribocil A的结合更强,与实验数据一致.
- 利博B结合的自由能量场景类似于道,而利博A则呈现出崎的场景.
- 连接物通过绑定口袋的"前门"的非本地 π-π 堆叠与 рибо交换机基相互作用,以方便进入和定位.
结论:
- 该研究揭示了Ribosil A和B的独特结合机制和亲和力,这是由于它们的自由能量格局的差异所驱动的.
- 非本地 π-π 堆在引导连接体到结合点方面发挥着作用,随后被本地堆取代.
- 确定了一个替代的"后门"路径,尽管它涉及克服连接体旋转的能量障碍.
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