适体
链霉素
氢键
化学
分子动力学
分子
结晶学
伞式取样
结合能
核糖核酸
计算化学
生物化学
生物
抗生素
有机化学
物理
原子物理学
基因
遗传学
作者
Thomas A. Nick,Tiago Espinosa de Oliveira,Dominik W. Pilat,Felix Spenkuch,Hans‐Jürgen Butt,Mark Helm,Paulo Augusto Netz,Rüdiger Berger
标识
DOI:10.1021/acs.jpcb.6b02440
摘要
Here we investigated the stability of an aptamer, which is formed by two RNA strands and binds the antibiotic streptomycin. Molecular dynamics simulations in aqueous solution confirmed the geometry and the pattern of hydrogen bond interactions that was derived from the crystal structure (1NTB). The result of umbrella sampling simulations indicated a favored streptomycin binding with a free energy of ΔGbind° = −101.7 kJ mol–1. Experimentally, the increase in oligonucleotide stability upon binding of streptomycin was probed by single-molecule force spectroscopy. Rate dependent force spectroscopy measurements revealed a decrease in the natural off-rate (koff-COMPLEX = 0.22 ± 0.16 s–1) for the aptamer–streptomycin complex compared to the aptamer having an empty binding pocket (koff-APTAMER = 0.49 ± 0.11 s–1). This decrease in the natural off-rate corresponds to a decrease in the Gibbs free energy of ΔΔGsheer ≈ −3.4 kJ mol–1. The simulated binding pattern and the experimental results led to the conclusion that hydrogen bonds between both RNA strands mainly contribute to the decrease in natural off-rate of the aptamer system studied.
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