Molecular dynamics simulation of melittin in a dimyristoylphosphatidylcholine bilayer membrane
Molecular dynamics simulation of melittin in a dimyristoylphosphatidylcholine bilayer membrane
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DOI：
10.1016/s0006-3495(98)77604-0
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发表时间：
1998-10-01
影响因子：
3.4
通讯作者：
Roux, B
中科院分区：
文献类型：
--
作者：
Bernèche, S;Nina, M;Roux, B
利用分子动力学方法研究了蜂毒肽在二肉豆蔻酰磷脂酰胆碱（DMPC）双层膜中的运动轨迹。蜂毒肽是一种存在于蜜蜂毒液中的两亲性小肽，对细胞膜的溶解有显著的作用。该肽最初平行于膜-溶液界面区域，呈α-螺旋构象，N-末端未质子化。固态核磁共振（NMR）和偏振衰减全内反射傅里叶变换红外（PATIR-FTIR）的蜂毒肽的性能计算的轨迹，以表征相对于双层的肽的取向。位于螺旋疏水部分的残基Lys（7）和C-末端亲水部分的残基Lys（23）、Arg（24）、Gln（25）和Gln（26）与水分子和脂质的酯羰基形成氢键，表明它们对双层中螺旋的稳定性有重要贡献。脂酰基链紧密堆积在蜂毒肽周围，有助于与膜的稳定结合。计算出的密度分布和顺序参数的脂质酰基链的平均分子动力学轨迹表明，蜂毒肽的膜上的两层的影响。蜂毒肽在上层中的存在导致有利于水渗透通过下层的双层的局部变薄。在膜表面的蜂毒肽协会所涉及的精力充沛的因素，其特征在于使用一个隐式的平均场模型，其中的膜和周围的溶剂被表示为无结构的连续介质材料。通过数值求解Poisson-Bolztmann方程得到的结果与详细的动力学定性一致。蜂毒肽的N-末端的质子化状态的影响进行检查。在600 ps后，蜂毒肽的N-末端被质子化，并且该轨迹持续400 ps，这导致水分子进入双层的重要渗透。这些观察结果提供了深入了解蜂毒素如何与膜相互作用和机制，它增强了他们的裂解。
Molecular dynamics trajectories of melittin in an explicit dimyristoyl phosphatidylcholine (DMPC) bilayer are generated to study the details of lipid-protein interactions at the microscopic lever. Melittin, a small amphipathic peptide round in bee venom, is known to have a pronounced effect on the lysis of membranes. The peptide is initially set parallel to the membrane-solution interfacial region in an a-helical conformation with unprotonated N-terminus. Solid-state nuclear magnetic resonance (NMR) and polarized attenuated total internal reflectance Fourier transform infrared (PATIR-FTIR) properties of melittin are calculated from the trajectory to characterize the orientation of the peptide relative to the bilayer. The residue Lys(7) located in the hydrophobic moiety of the helix and residues Lys(23), Arg(24), Gln(25), and Gln(26) at the C-terminus hydrophilic form hydrogen bonds with water molecules and with the ester carbonyl groups of the lipids, suggesting their important contribution to the stability of the helix in the bilayer. Lipid acyl chains are closely packed around melittin, contributing to the stable association with the membrane. Calculated density profiles and order parameters of the lipid acyl chains averaged over the molecular dynamics trajectory indicate that melittin has effects on both layers of the membrane. The presence of melittin in the upper layer causes a local thinning of the bilayer that favors the penetration of water through the lower layer. The energetic factors involved in the association of melittin at the membrane surface are characterized using an implicit mean-field model in which the membrane and the surrounding solvent are represented as structureless continuum dielectric material. The results obtained by solving the Poisson-Bolztmann equation numerically are in qualitative agreement with the detailed dynamics. The influence of the protonation state of the N-terminus of melittin is examined. After 600 ps, the N-terminus of melittin is protonated and the trajectory is continued for 400 ps, which leads to an important penetration of water molecules into the bilayer. These observations provide insights into how melittin interacts with membranes and the mechanism by which it enhances their lysis.