Membrane assembly of simple helix homo-oligomers studied via molecular dynamics simulations
Membrane assembly of simple helix homo-oligomers studied via molecular dynamics simulations
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DOI：
10.1529/biophysj.106.095216
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发表时间：
2007-02-01
影响因子：
3.4
通讯作者：
Brooks, Charles L., III
中科院分区：
文献类型：
--
作者：
Bu, Lintao;Im, Wonpil;Brooks, Charles L., III
通过将广义Born隐式膜模型与副本交换分子动力学模拟相结合，研究了简单跨膜螺旋低聚物的组装，采样了不同齐聚状态的构象空间和天然低聚构象。我们的方法被应用于预测三种蛋白质-血糖素A、M2质子通道和磷蛋白的跨膜螺旋结构-仅使用肽序列和天然齐聚状态信息。在每一种情况下，该方法都能复制出与现有实验结构数据非常一致的天然构象。因此，我们的方法对于预测其他多肽跨膜区的天然结构也是有用的。当我们忽略对天然齐聚状态的实验限制，仅基于序列和简单的能量考虑尝试从头预测结构和齐聚状态时，我们确定五聚体是最稳定的磷蛋白齐聚物。然而，对于血糖素A和M2质子通道，我们倾向于预测较高的低聚物更稳定。我们的研究表明，当观察到的齐聚状态作为约束条件时，可以实现对跨膜螺旋低聚物结构的可靠预测，但需要进一步努力才能对结构和低聚状态进行从头预测。
The assembly of simple transmembrane helix homo-oligomers is studied by combining a generalized Born implicit membrane model with replica exchange molecular dynamics simulations to sample the conformational space of various oligomerization states and the native oligomeric conformation. Our approach is applied to predict the structures of transmembrane helices of three proteins-glycophorin A, the M2 proton channel, and phospholamban-using only peptide sequence and the native oligomerization state information. In every case, the methodology reproduces native conformations that are in good agreement with available experimental structural data. Thus, our method should be useful in the prediction of native structures of transmembrane domains of other peptides. When we ignore the experimental constraint on the native oligomerization state and attempt de novo prediction of the structure and oligomerization state based only on sequence and simple energetic considerations, we identify the pentamer as the most stable oligomer for phospholamban. However, for the glycophorin A and the M2 proton channels, we tend to predict higher oligomers as more stable. Our studies demonstrate that reliable predictions of the structure of transmembrane helical oligomers can be achieved when the observed oligomerization state is imposed as a constraint, but that further efforts are needed for the de novo prediction of both structure and oligomeric state.