Folding and insertion thermodynamics of the transmembrane WALP peptide
Folding and insertion thermodynamics of the transmembrane WALP peptide
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DOI：
10.1063/1.4935487
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发表时间：
2015-12-28
影响因子：
4.4
通讯作者：
Karttunen, Mikko
中科院分区：
文献类型：
--
作者：
Bereau, Tristan;Bennett, W. F. Drew;Karttunen, Mikko
大多数完整膜蛋白的锚点由一个或几个跨越脂质双分子层的螺旋组成。WALP肽GWW(LA)(n)(L)WWA是一种常用的螺旋模型，用于研究蛋白质插入和折叠的基本原理，以及膜内螺旋-螺旋结合。它的结构特性已经在大量的实验和模拟研究中得到阐明。在这项结合粗粒度和原子模拟的研究中，我们探讨了单个WALP肽的热力学，重点关注了水膜界面上的插入，以及在水和膜中的折叠。表征肽插入膜的平均力势在不同的多肽和三个力场中表现出质量上相似的行为。然而，与原子模拟和可选的PLUM力场相比，Martini力场在吸附界面状态下表现出明显的二次最小值，甚至可能成为全局最小值。尽管这两个粗粒度模型再现了单个氨基酸侧链插入的自由能，但它们都低估了完整肽的相应值（与原子模拟相比），这暗示了在残馀水平之外的合作物理。两种环境下的WALP折叠表明，螺旋结构是最稳定的结构，尽管相对稳定性和链长依赖性不同。(C) 2015 AIP出版有限责任公司
The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA)(n)(L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural properties have been illuminated in a large number of experimental and simulation studies. In this combined coarse-grained and atomistic simulation study, we probe the thermodynamics of a single WALP peptide, focusing on both the insertion across the water-membrane interface, as well as folding in both water and a membrane. The potential of mean force characterizing the peptide's insertion into the membrane shows qualitatively similar behavior across peptides and three force fields. However, the Martini force field exhibits a pronounced secondary minimum for an adsorbed interfacial state, which may even become the global minimum-in contrast to both atomistic simulations and the alternative PLUM force field. Even though the two coarse-grained models reproduce the free energy of insertion of individual amino acids side chains, they both underestimate its corresponding value for the full peptide (as compared with atomistic simulations), hinting at cooperative physics beyond the residue level. Folding of WALP in the two environments indicates the helix as the most stable structure, though with different relative stabilities and chain-length dependence. (C) 2015 AIP Publishing LLC.