Computer simulation of partitioning of ten pentapeptides Ace-WLXLL at the cyclohexane/water and phospholipid/water interfaces.
Computer simulation of partitioning of ten pentapeptides Ace-WLXLL at the cyclohexane/water and phospholipid/water interfaces.
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DOI：
10.1186/1471-2091-6-30
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发表时间：
2005-12-20
期刊：
影响因子：
--
通讯作者：
Tieleman DP
中科院分区：
文献类型：
--
作者：
Aliste MP;Tieleman DP
多肽-膜相互作用在膜蛋白的结合、分配和折叠、抗菌肽和融合肽的活性以及许多其他过程中起着关键作用。为了更好地理解这种相互作用的热力学，White和Wimley创建了一个界面疏水性标度，该标度基于一系列合成肽(Ace-WLXLL，其中X是20种天然氨基酸中的任何一种)从水到辛醇或脂双层的转移自由能(White和Wimley(1996)NAT)。结构。比奥尔。3,842-848)。在这项研究中，我们使用恒压和恒面积系综，在两个膜模拟界面：水-环己烷(10 Ns)和完全溶剂化的二油酰磷脂酰胆碱(DOPC)双层(50 Ns)中对十个具有代表性的多肽(X=D，K，R，N，A，T，S，I，F和W)进行了分子动力学模拟。我们重点研究了这十个多肽在环己烷/水和脂类/水界面的分配。多肽在环己烷/水界面上迅速平衡(~lt；2 ns)和分配。X3客体残基的平均取向取决于侧链的性质。在DOPC/水界面，动力学要慢得多，并且很难在50 ns的时间尺度上实现收敛。尽管如此，所有的多肽都以1-2 nm的宽度分布在脂质/水界面。这些多肽具有广泛的侧链和主链取向，并且对单位细胞的面积只有很小的影响。平均而言，疏水性客体残基比亲水性残基在疏水核心中分配得更深。在某些情况下，多肽穿透得足够深，从而在一定程度上影响DOPC中C=C双键的分布。在水/环己烷和水/脂模拟中，与W1和L5相比，X3客体残基的相对分布相似。快照显示了这两种环境中的大部分扩展主干构象。在0.66 nm~2的恒定面积模拟和在恒定压力下的模拟之间几乎没有差别，后者产生的平均面积大致相同，为0.66 nm~2。这些多肽被设计成具有扩展的构象，这一点得到了模拟的证实。X3侧链的分布取决于其性质，可以通过分子动力学模拟确定。多肽在磷脂-水界面上运动的时间尺度太长，不能直接计算实验测得的疏水性尺度来检验和改进模拟参数。这在水/环己烷界面上应该是可能的，并且很可能在将来对于磷脂/水情况变得可行。
Peptide-membrane interactions play a key role in the binding, partitioning and folding of membrane proteins, the activity of antimicrobial and fusion peptides, and a number of other processes. To gain a better understanding of the thermodynamics of such interactions, White and Wimley created an interfacial hydrophobicity scale based of the transfer free energy from water to octanol or lipid bilayers of a series of synthetic peptapeptides (Ace-WLXLL, with X being any of the twenty natural amino acids) (White and Wimley (1996) Nat. Struct. Biol. 3, 842–848). In this study, we performed molecular dynamics simulations of a representative set of ten of these peptides (X = D, K, R, N, A, T, S, I, F and W) in two membrane mimetic interfaces: water-cyclohexane (10 ns) and a fully solvated dioleoylphosphatidylcholine (DOPC) bilayer (50 ns) using both constant pressure and constant area ensembles. We focus on partitioning of the ten peptides at the cyclohexane/water and lipid/water interfaces. The peptides rapidly equilibrate (< 2 ns) and partition at the cyclohexane/water interface. The X3 guest residue assumes average orientations that depend on the nature of the side chain. At the DOPC/water interface, dynamics is much slower and convergence is difficult to achieve on a 50 ns timescale. Nonetheless, all peptides partition to the lipid/water interface with distributions with widths of 1–2 nm. The peptides assume a broad range of side chain and backbone orientations and have only a small effect on the area of the unit cell. On average, hydrophobic guest residues partition deeper into the hydrophobic core than hydrophilic residues. In some cases the peptides penetrate sufficiently deep to somewhat affect the distribution of the C=C double bond in DOPC. The relative distribution of the X3 guest residue compared to W1 and L5 is similar in the water/cyclohexane and water/lipid simulations. Snapshots show mostly extended backbone conformations in both environments. There is little difference between simulations at a constant area of 0.66 nm2 and simulations at constant pressure that approximately yield the same average area of 0.66 nm2. These peptides were designed to assume extended conformations, which is confirmed by the simulations. The distribution of the X3 side chain depends on its nature, and can be determined from molecular dynamics simulations. The time scale of peptide motion at a phospholipids-water interface is too long to directly calculate the experimentally measured hydrophobicity scale to test and improve the simulation parameters. This should be possible at the water/cyclohexane interface and likely will become feasible in the future for the phospholipids/water case.
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影响因子：
3.3
作者：
Anézo, C;de Vries, AH;Marrink, SJ
通讯作者：
Marrink, SJ
影响因子：
3.4
作者：
Hoff, B;Strandberg, E;Posten, C
通讯作者：
Posten, C
影响因子：
4.4
作者：
Shirts, MR;Pande, VS
通讯作者：
Pande, VS
影响因子：
3.4
作者：
Lensink, MF;Christiaens, B;Rosseneu, M
通讯作者：
Rosseneu, M
影响因子：
2.9
作者：
HERMANS, J;BERENDSEN, HJC;POSTMA, JPM
通讯作者：
POSTMA, JPM