The Curvature Induction of Surface-Bound Antimicrobial Peptides Piscidin 1 and Piscidin 3 Varies with Lipid Chain Length.
The Curvature Induction of Surface-Bound Antimicrobial Peptides Piscidin 1 and Piscidin 3 Varies with Lipid Chain Length.
复制标题
DOI：
10.1007/s00232-014-9733-1
复制
发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Pastor RW
中科院分区：
文献类型：
--
作者：
Perrin BS Jr;Sodt AJ;Cotten ML;Pastor RW
抗菌肽 (AMP) 破坏膜的初始步骤涉及以表面结合 (S) 方向与细菌膜结合。为了评估脂质成分对 S 状态的影响，在 4 种不同的双层中对 AMP piscidin 1 (p1) 和 piscidin 3 (p3) 进行了分子动力学模拟：3:1 DMPC/DMPG、3:1 POPC/POPG、1:1 POPE/POPG 和 4:1 POPC/胆固醇。在所有情况下，添加 1:40 piscidin 都会导致双层变薄，但 DMPC/DMPG 的变薄程度最小。这些肽还插入 DMPC/DMPG 最深处，跨越从双层中平面到头部基团的区域，从而仅轻微破坏酰基链。相比之下，肽在含有棕榈酰-油酰的膜中插入的深度较浅，不会到达中平面，并且会显着破坏链；即，相邻的酰基链在肽下方弯曲，形成篮状构象。根据模拟压力分布计算的曲率自由能导数表明，肽在具有棕榈酰基和油酰基链的膜中产生正曲率，而在具有肉豆蔻酰基链的膜中产生负曲率。使用连续弹性模型预测的曲率感应遵循相同的趋势，尽管效果较弱并且在 POPC/POPG 中获得了较小的负曲率感应。这些结果并不直接说明插入 (I) 态的相对稳定性或孔形成的容易程度，这需要 S 和 I 态之间的自由能路径。尽管如此，它们确实强调了脂质成分和酰基链堆积的重要性。
The initial steps of membrane disruption by antimicrobial peptides (AMPs) involve binding to bacterial membranes in a surface-bound (S) orientation. To evaluate the effects of lipid composition on the S state, molecular dynamics simulations of the AMPs piscidin 1 (p1) and piscidin 3 (p3) were carried out in 4 different bilayers: 3:1 DMPC/DMPG, 3:1 POPC/POPG, 1:1 POPE/POPG, and 4:1 POPC/cholesterol. In all cases, the addition of 1:40 piscidin caused thinning of the bilayer, though thinning was least for DMPC/DMPG. The peptides also insert most deeply into DMPC/DMPG, spanning the region from the bilayer midplane to the head groups, and thereby only mildly disrupting the acyl chains. In contrast, the peptides insert less deeply in the palmitoyl-oleoyl containing membranes, do not reach the midplane, and substantially disrupt the chains; i.e., the neighboring acyl chains bend under the peptide, forming a basket-like conformation. Curvature free energy derivatives calculated from the simulation pressure profiles reveal that the peptides generate positive curvature in membranes with palmitoyl and oleoyl chains but negative curvature in those with myristoyl chains. Curvature inductions predicted with a continuum elastic model follow the same trends, though the effect is weaker and a small negative curvature induction is obtained in POPC/POPG. These results do not directly speak to the relative stability of the inserted (I) states or ease of pore formation, which requires the free energy pathway between the S and I states. Nevertheless, they do highlight the importance of lipid composition and acyl chain packing.
登录
查看更多内容
影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
3.4
作者：
GRUNER, SM;PARSEGIAN, VA;RAND, RP
通讯作者：
RAND, RP
影响因子：
3.4
作者：
Meleard, P;Gerbeaud, C;Bothorel, P
通讯作者：
Bothorel, P
影响因子：
3.4
作者：
Fuller, N;Benatti, CR;Rand, RP
通讯作者：
Rand, RP
影响因子：
2.9
作者：
HOOVER, WG
通讯作者：
HOOVER, WG