利博开关与自然干的结合机制通过基于McMD的动态对接模拟来阐明
Gert-Jan Bekker1, Yoshifumi Fukunishi2, Junichi Higo3
1Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
ACS omega
|January 29, 2024
概括
研究人员探索了flavin mononucleotide riboswitch是如何结合利博弗拉 (维生素B2) 的. 通过使用先进的模拟,他们揭示了一个动态机制,即 рибофлавин在到达其隐藏的结合部位之前,通过一个通道进入.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 弗拉单核酸 (FMN) рибо开关在致病细菌中普遍存在,这使得它们成为有希望的抗生素标.
- 尽管FMN核糖开关结合了利博氨酸 (维生素B2),但其精确的结合机制仍然难以捉摸,尽管解决了复杂的结构.
研究的目的:
- 阐明 riboflavin 与 FMN рибо交换机 胺体域的动态结合机制.
- 为了确定关键的步骤和构造变化涉及连接体进入和稳定在线杆切换器内.
主要方法:
- 使用基于多规范分子动力学 (McMD) 的动态对接协议.
- 模拟了结合过程,从FMN рибо交换机的aptamer的apo状态开始.
- 采用了精细化阶段来区分原生结合配置和短暂相互作用.
主要成果:
- 确定了P4-P6接口的初始结合事件,涉及核酸U61和G62,作为连接体通道.
- 观察到的 riboflavin (RBF) 在形状变化允许通过之前在这个通道停留.
- 在关口打开后,确定了RNA中的最终结合部位,涉及核酸A48,A49和A85.
结论:
- 绑定机制涉及一个动态的过程,最初的网关相互作用,然后进入一个深,隐藏的绑定口袋.
- 这种详细了解FMN рибо开关- рибо氨酸相互作用对于合理的针对细菌病原体的抗生素设计至关重要.
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