In silico partitioning and transmembrane insertion of hydrophobic peptides under equilibrium conditions.
In silico partitioning and transmembrane insertion of hydrophobic peptides under equilibrium conditions.
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DOI：
10.1021/ja204042f
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发表时间：
2011-10-05
影响因子：
15
通讯作者：
Ulmschneider, Martin B.
中科院分区：
文献类型：
--
作者：
Ulmschneider, Jakob P.;Smith, Jeremy C.;White, Stephen H.;Ulmschneider, Martin B.
新生的跨膜（TM）多肽片段被识别，并插入到脂质双层的细胞translocon机器。的识别规则，描述了一个生物疏水性规模，强烈相关的物理疏水性规模，描述了从水中插入TM螺旋的自由能。然而，物理和生物尺度之间的确切关系是未知的，因为溶解度的问题限制了我们的能力，通过实验测量直接分配的疏水肽跨脂质膜。在这里，我们使用微秒分子动力学（MD）模拟，其中允许不同长度的单体聚亮氨酸片段自发地分区进出脂质双层。这种方法直接揭示了平衡态的所有状态。对于所研究的疏水肽，只发现了表面结合和跨膜插入螺旋，插入自由能直接由这些状态的相对占有率得到。未观察到水溶性状态，与疏水肽的一般不溶性一致。该方法还允许确定分配途径和动力学。令人惊讶的是，转移自由能似乎是独立的温度，这意味着表面到双层肽插入是一个零熵的过程。我们发现，分区自由能的聚亮氨酸段强烈相关的值从translocon实验，但揭示了一个系统的转变，有利于较短的肽，这表明translocon-双层分区是不等价的，但有关的自发表面-双层分区。
Nascent transmembrane (TM) polypeptide segments are recognized and inserted into the lipid bilayer by the cellular translocon machinery. The recognition rules, described by a biological hydrophobicity scale, correlate strongly with physical hydrophobicity scales that describe the free energy of insertion of TM helices from water. However, the exact relationship between the physical and biological scales is unknown, because solubility problems limit our ability to measure experimentally the direct partitioning of hydrophobic peptides across lipid membranes. Here we use microsecond molecular dynamics (MD) simulations in which monomeric poly-leucine segments of different lengths are allowed to partition spontaneously into and out of lipid bilayers. This approach directly reveals all states populated at equilibrium. For the hydrophobic peptides studied here, only surface bound and transmembrane inserted helices are found. The free energy of insertion is directly obtained from the relative occupancy of these states. A water soluble state was not observed, consistent with the general insolubility of hydrophobic peptides. The approach further allows determination of the partitioning pathways and kinetics. Surprisingly, the transfer free energy appears to be independent of temperature, which implies that surface-to-bilayer peptide insertion is a zero-entropy process. We find that the partitioning free energy of the polyleucine segments correlates strongly with values from translocon experiments, but reveals a systematic shift favouring shorter peptides, suggesting that translocon-to-bilayer partitioning is not equivalent, but related to spontaneous surface-to-bilayer partitioning.
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影响因子：
3.3
作者：
Junne T;Kocik L;Spiess M
通讯作者：
Spiess M
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
6.3
作者：
BERENDSEN, HJC;VANDERSPOEL, D;VANDRUNEN, R
通讯作者：
VANDRUNEN, R
DOI：
10.1073/pnas.1012758108
发表时间：
2011-03-01
影响因子：
11.1
作者：
Gumbart, James;Chipot, Christophe;Schulten, Klaus
通讯作者：
Schulten, Klaus
影响因子：
5.6
作者：
Meijberg, W;Booth, PJ
通讯作者：
Booth, PJ