分子动力学模拟研究A1408G突变对核糖体16S rRNA片段的影响

Molecular Dynamics Studies on the Structure of 16S rRNA Fragment Affected by A1408G Mutation

利用分子动力学模拟方法,研究了原核生物核糖体小亚基中的16SrRNA片段与氨基糖苷类抗生素巴龙霉素复合物结构的柔性.结果表明,16SrRNA片段中的1408位点的腺嘌呤(A)突变为鸟嘌呤(G),改变了与tRNA中反密码子环识别相关的2个腺嘌呤A1492和A1493的空间构象,阻碍了氨基糖苷类抗生素与核糖体的结合,从而影响原核生物蛋白转录过程.模拟结果与实验测定的晶体结构相吻合,可为基于核糖体16SrRNA的药物分子设计提供较可靠的结构信息.

Using molecular dynamics simulation,the flexibility of 16S rRNA complexed with paromomycin was studied. The results indicate that the position 1408 of 16S rRNA in ribosome is very important. The substitution of adenine for guanine will change the position of two adenines（ A1492 and A1493） which are involved in tRNA anticodon loop recognition,affecting the binding of aminoglycosidic antibiotics and protein translation in prokaryota. The simulation results show a good agreement with experimental data,which provided some structural information for the drug design based on 16S rRNA in ribosome.