Extending the structure of an ABC transporter to atomic resolution: Modeling and simulation studies of MsbA
Extending the structure of an ABC transporter to atomic resolution: Modeling and simulation studies of MsbA
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DOI：
10.1021/bi027337t
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发表时间：
2003-04-08
期刊：
影响因子：
2.9
通讯作者：
Sansom, MSP
中科院分区：
文献类型：
--
作者：
Campbell, JD;Biggin, PC;Sansom, MSP
从基于低分辨结构的Calpha迹(PDB编码1JSQ)开始，分子建模和模拟方法被用来从大肠杆菌中产生原核ABC转运蛋白MSBA的完整模型。MSBA与哺乳动物转运蛋白如P-糖蛋白和TAP具有同源性，因此具有一定的生物医学价值。MSBA模型的质量使用分子动力学模拟和静态结构分析相结合的方法进行评估。这些结果表明，MSBA所采用的方法可能对从膜蛋白的低分辨晶体结构中产生所有原子模型具有普遍的实用价值。对MSBA模型插入完全溶剂化辛烷板(模拟膜环境)的分子动力学模拟表明，虽然单体相对稳定，但二聚体是不稳定的，并且在纳秒时间尺度上经历了显著的构象漂移。这表明MSBA晶体二聚体在体内可能与MSBA二聚体不对应。在现有实验数据的背景下，讨论了二聚体的另一种模型。
Molecular modeling and simulation approaches have been use to generate a complete model of the prokaryotic ABC transporter MsbA from Escherichia coli, starting from the low-resolution structure-based Calpha trace (PDB code 1JSQ). MsbA is of some biomedical interest as it is homologous to mammalian transporters such as P-glycoprotein and TAP. The quality of the MsbA model is assessed using a combination of molecular dynamics simulations and static structural analysis. These results suggest that the approach adopted for MsbA may be of general utility for generating all atom models from low-resolution crystal structures of membrane proteins. Molecular dynamics simulations of the MsbA model inserted in a fully solvated octane slab (a membrane mimetic environment) reveal that while the monomer is relatively stable, the dimer is unstable and undergoes significant conformational drift on a nanosecond time scale. This suggests that the MsbA crystal dimer may not correspond to the MsbA dimer in vivo. An alternative model of the dimer is discussed in the context of available experimental data.