计算和实验分析汇聚在一起,揭示出一个连贯而又可塑的aptamer结构,可以控制化学反应
Tianjiao Wang1, Julie A Hoy, Monica H Lamm
1Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 50011, USA.
Journal of the American Chemical Society
|September 26, 2009
概括
像马拉绿色的阿普塔默一样的阿普塔默可以保护绑定的目标免受化学修饰的影响. 这种保护是可逆的,证明了aptamer的结构灵活性和选择性分子屏蔽的潜力.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 计算化学的计算化学
背景情况:
- 胺是短核酸,以其在溶液中的结构灵活性而闻名.
- 许多体酶通过诱导适合机制结合目标.
- 体灵活性对体相互作用完整性的影响尚不清楚.
研究的目的:
- 为了研究aptamer-target相互作用的结构完整性和保护能力.
- 使用马拉绿色体 (MGA) 作为研究目标保护的模型系统.
- 探索结构灵活性在阿普坦胺-标结合中的作用及其功能后果.
主要方法:
- 使用MGA及其目标,马拉绿 (MG) 的实验性保护测定.
- 以寡核酸为媒介的目标保护的逆转.
- 对MGA-MG复合体进行计算空腔分析和分子动力学模拟.
- 使用单基变化的MGA变体进行实验验证.
主要成果:
- 在几天内,MGA成功地保护了结合的MG免受氧化.
- 保护被补充的寡核酸逆转,表明了动态结合接口.
- 计算分析预测了氧化剂 (例如,OH-) 从MG结合部位的硬质排除.
- 实验结果证实了计算预测,并证明了序列变化的效果.
结论:
- 该MGA-MG接口足够稳定,以防止小分子透,但足够动态的基础配对相互作用.
- 适应剂的结构灵活性允许控制对目标分子上特定化学组的访问.
- 能够被设计为选择性地保护小分子免受化学修饰的aptamers,建议治疗和诊断应用.
相关概念视频
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Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...