Solid-State NMR Ensemble Dynamics as a Mediator between Experiment and Simulation
Solid-State NMR Ensemble Dynamics as a Mediator between Experiment and Simulation
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DOI：
10.1016/j.bpj.2011.02.063
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发表时间：
2011-06-22
影响因子：
3.4
通讯作者：
Im, Wonpil
中科院分区：
文献类型：
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作者：
Kim, Taehoon;Jo, Sunhwan;Im, Wonpil
固体核磁共振是描述膜蛋白和多肽在其天然膜双层环境中取向的一种强有力的技术。用半静态刚体模型，如标记丙氨酸几何分析(GALA)方法，研究了不同单程跨膜(TM)螺旋的取向。然而，这些TM螺旋的动态信息可能与重要的生物学功能有关，但半静态模型可能会遗漏或误解这些信息。我们通过使用具有DOS限制势的多个构象模型确定了WALP23的结构集合，研究了WALP23在二肉豆蔻基甘油磷胆碱隐含膜中的定位。当使用单个构象时，得到的螺旋方向(倾斜角(Tau)为5.6+/-3.2度，旋转角(Rho)为141.8+/-40.6度)与GALA方法确定的类似。然而，随着构象数目的增加，WALP23系综结构的倾角变大(26.9+/-6.7度)，这与以前的分子动力学模拟结果很好地吻合。此外，系综结构分布与二维自由能表面表现出很好的一致性，这是WALP23的S陶和Rho的函数。这些结果表明，SS核磁共振系综动力学提供了一种从SS核磁共振观测数据中提取TM螺旋的取向和动力学信息的方法，并解释了分子动力学模拟与基于GALA的DOS数据解释之间的差异。
Solid-state NMR (SSNMR) is a powerful technique to describe the orientations of membrane proteins and peptides in their native membrane bilayer environments. The deuterium (H-2) quadrupolar splitting (DOS), one of the SSNMR observables, has been used to characterize the orientations of various single-pass transmembrane (TM) helices using a semistatic rigid-body model such as the geometric analysis of labeled alanine (GALA) method. However, dynamic information of these TM helices, which could be related to important biological function, can be missing or misinterpreted with the semistatic model. We have investigated the orientation of WALP23 in an implicit membrane of dimyristoylglycerophosphocholine by determining an ensemble of structures using multiple conformer models with a DOS restraint potential. When a single conformer is used, the resulting helix orientation (tilt angle (tau) of 5.6 +/- 3.2 degrees and rotation angle (rho) of 141.8 +/- 40.6 degrees) is similar to that determined by the GALA method. However, as the number of conformers is increased, the tilt angles of WALP23 ensemble structures become larger (26.9 +/- 6.7 degrees), which agrees well with previous molecular dynamics simulation results. In addition, the ensemble structure distribution shows excellent agreement with the two-dimensional free energy surface as a function of WALP23's tau and rho. These results demonstrate that SSNMR ensemble dynamics provides a means to extract orientational and dynamic information of TM helices from their SSNMR observables and to explain the discrepancy between molecular dynamics simulation and GALA-based interpretation of DOS data.