Simulation studies of alamethicin-bilayer interactions
Simulation studies of alamethicin-bilayer interactions
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DOI：
10.1016/s0006-3495(97)78701-0
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发表时间：
1997-02-01
影响因子：
3.4
通讯作者：
Sansom, MSP
中科院分区：
文献类型：
--
作者：
Biggin, PC;Breed, J;Sansom, MSP
丙甲霉素是一种α-螺旋肽，形成电压激活离子通道。实验数据表明，通道形成发生通过电压依赖性插入丙甲霉素螺旋到脂质双层，然后通过自组装插入的螺旋，形成一个平行的螺旋束。丙甲霉素螺旋围绕其中心脯氨酸残基的扭结角的变化也被认为在通道门控中起作用。通过模拟退火和受约束的分子动力学产生的丙甲霉素螺旋采用类似于X射线晶体结构中的扭结角，即使这样的模拟从理想化的未扭结螺旋开始。这表明扭结的螺旋代表了分子的稳定构象。在一个简单的双层模型和跨双层电压差的存在下，分子动力学模拟被用来探索螺旋插入的可能机制。双分子层由疏水势表示。丙甲霉素螺旋在没有跨双层电压的情况下自发插入。施加顺式正电压减少了插入时间。螺旋扭结角在模拟过程中波动。螺旋的插入与平均扭结角的减小有关，因此有助于丙甲霉素分子跨越双层。根据丙甲霉素通道门控模型对模拟结果进行了讨论。
Alamethicin is an alpha-helical peptide that forms voltage-activated ion channels. Experimental data suggest that channel formation occurs via voltage-dependent insertion of alamethicin helices into lipid bilayers, followed by self-assembly of inserted helices to form a parallel helix bundle. Changes in the kink angle of the alamethicin helix about its central proline residue have also been suggested to play a role in channel gating. Alamethicin helices generated by simulated annealing and restrained molecular dynamics adopt a kink angle similar to that in the x-ray crystal structure, even if such simulations start with an idealized unkinked helix. This suggests that the kinked helix represents a stable conformation of the molecule. Molecular dynamics simulations in the presence of a simple bilayer model and a transbilayer voltage difference are used to explore possible mechanisms of helix insertion. The bilayer is represented by a hydrophobicity potential. An alamethicin helix inserts spontaneously in the absence of a transbilayer voltage. Application of a cis positive voltage decreases the time to insertion. The helix kink angle fluctuates during the simulations. insertion of the helix is associated with a decrease in the mean kink angle, thus helping the alamethicin molecule to span the bilayer. The simulation results are discussed in terms of models of alamethicin channel gating.