Free energy of WALP23 dimer association in DMPC, DPPC, and DOPC bilayers
Free energy of WALP23 dimer association in DMPC, DPPC, and DOPC bilayers
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DOI：
10.1016/j.chemphyslip.2013.02.001
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发表时间：
2013-04-01
影响因子：
3.4
通讯作者：
Tieleman, D. Peter
中科院分区：
文献类型：
--
作者：
Castillo, Norberto;Monticelli, Luca;Tieleman, D. Peter
MARTINI粗粒度模型用于深入了解WALP 23螺旋在三种不同脂质膜中的关联：DMPC，DPPC和DOPC。描述嵌入不同脂质双层中的两个WALP 23螺旋的缔合的平均力的势表明没有缔合屏障，并且相对于完全解离状态，缔合状态的稳定性超过20 kJ mol（-1）。关联性在DMPC中最强，其次是DPPC和DOPC。螺旋-螺旋缔合似乎在所有脂质双层中均是有利的，而熵贡献仅在DMPC脂质中存在显著的正疏水错配时才有利。考虑到模拟的粗粒度性质，对此的解释需要小心，但热力学量的符号与（AALALAA）（3）肽二聚化的实验测量一致，并且观察到的缔合自由能在实验范围内。蛋白质-蛋白质和脂质-脂质相互作用似乎都强烈地有利于蛋白质二聚化，而二聚体和脂质之间的相互作用相对于两个分离的单体和脂质之间的相互作用是不利的。具有反平行取向的二聚体似乎比平行二聚体更有利，特别是在更大的疏水性错配的条件下，但阐明这可能需要模拟螺旋的详细起源，其中有关于二聚体的结构数据。我们使用新的免费分析程序分析3D密度，膜顺序和膜厚度图。虽然这些性质对于每种脂质略有不同，但对于脂质密度，扰动延伸至约1 nm，对于有序性，扰动延伸至约2 nm，对于厚度，扰动延伸至约2.5 nm。一个显著的特征是螺旋周围系统密度波动的出现和程度。(C)2013爱思唯尔爱尔兰有限公司版权所有。
The MARTINI coarse-grained model is used to gain insight into the association of WALP23 helices in three different lipid membranes: DMPC, DPPC and DOPC. Potentials of mean force describing the association of two WALP23 helices embedded in different lipid bilayers indicate no barrier of association and a stabilization of more than 20 kJ mol(-1) of the associated state relative to the fully dissociated state. Association is strongest in DMPC, followed by DPPC and DOPC. Helix-helix association appears to be enthalpically favorable in all lipid bilayers, while the entropic contribution appears favorable only in the presence of significant positive hydrophobic mismatch, in DMPC lipids. The interpretation of this requires care given the coarse-grained nature of the simulations, but the sign of the thermodynamic quantities agrees with experimental measurements on dimerization of (AALALAA)(3) peptides and the observed association free energies are within the experimental range. Both protein-protein and lipid-lipid interactions appear to strongly favor protein dimerization, while the interactions between a dimer and lipid are unfavorable relative to the interactions between two separated monomers and lipids. Dimers with antiparallel orientation appear to be thermodynamically favored over parallel dimers, particularly in conditions of greater hydrophobic mismatch, but elucidating the detailed origin of this likely requires simulations of helices for which there is structural data on the dimer. We analyze 3D density, membrane order, and membrane thickness maps using new freely available analysis programs. Although these properties differ somewhat for each lipid, perturbations extend to about 1 nm for lipid density, similar to 2 nm for ordering and similar to 2.5 nm for thickness. A striking feature is the appearance and extent of systematic density fluctuations around the helices. (C) 2013 Elsevier Ireland Ltd. All rights reserved.