Structure of the antimicrobial β-hairpin peptide protegrin-1 in a DLPC lipid bilayer investigated by molecular dynamics simulation
Structure of the antimicrobial β-hairpin peptide protegrin-1 in a DLPC lipid bilayer investigated by molecular dynamics simulation
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DOI：
10.1016/j.bbamem.2006.11.015
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发表时间：
2007-03-01
影响因子：
3.4
通讯作者：
Kaznessis, Yiannis N.
中科院分区：
文献类型：
--
作者：
Khandelia, Himanshu;Kaznessis, Yiannis N.
对18个残基的β-发夹抗菌肽protegrin-1（PG-1，RGGRLCYCRRRFCVCVGR-NH 2）在完全水合的二月桂酰磷脂酰胆碱（DLPC）脂质双层中的全原子分子动力学模拟进行了研究。所报道的工作的目标是研究膜环境中肽的结构（以前仅在溶液中解决[R.L. Fahrner，T. Dieckmann，S.S.L. R.I.哈维格Lehrer，D. Eisenberg，J. Feigon，Protegrin-1的溶液结构，一种来自猪白细胞的广谱抗菌肽。Chemistry and Biology，3（1996）543-550]），并描述负责肽的膜结合性质的特定肽-膜相互作用。检测到肽的一种新的、以前未知的“踢”形构象，其中肽的C-末端β-链处的弯曲导致肽骨架在残基16-18处垂直于β-发夹平面延伸。该弯曲由TYR 7的极性肽侧链和GLY 17的未屏蔽骨架羰基氧原子之间的高度持久的氢键驱动。氢键的形成缓解了极性基团插入疏水膜芯的不利自由能。PG-1被锚定到膜的强静电结合的质子化的N-末端的肽的脂质头基团磷酸根阴离子。肽在膜中的取向及其对双层结构和动力学性质的影响与固态NMR测量结果非常一致[S。山口T. Hong，A. Waring，R.I. Lehrer，M. Hong，Solid-State NMR Investigations of Peptide-Lipid Interaction and Orientation of a b-Sheet Antimicrobial Peptide，Protegrin，Biochemistry，41（2002）9852-9862]。重要的是，从肽的不同初始取向开始的两个模拟收敛到肽相对于双层的相同的最终平衡取向。踢形构象只观察到在两个模拟之一。(c)2006 Elsevier B. V.保留所有权利。
All atom molecular dynamics simulations of the 18-residue beta-hairpin antimicrobial peptide protegrin-1 (PG-1, RGGRLCYCRRRFCVCVGR-NH2) in a fully hydrated dilauroylphosphatidylcholine (DLPC) lipid bilayer have been implemented. The goal of the reported work is to investigate the structure of the peptide in a membrane environment (previously solved only in solution [R.L. Fahrner, T. Dieckmann, S.S.L. Harwig, R.I. Lehrer, D. Eisenberg, J. Feigon, Solution structure of protegrin-1, a broad-spectrum antimicrobial peptide from porcine leukocytes. Chemistry and Biology, 3 (1996) 543-550]), and to delineate specific peptide-membrane interactions which are responsible for the peptide's membrane binding properties. A novel, previously unknown, "kick" shaped conformation of the peptide was detected, where a bend at the C-terminal beta-strand of the peptide caused the peptide backbone at residues 16-18 to extend perpendicular to the beta-hairpin plane. This bend was driven by a highly persistent hydrogen-bond between the polar peptide side-chain of TYR7 and the unshielded backbone carbonyl oxygen atom of GLY17. The H-bond formation relieves the unfavorable free energy of insertion of polar groups into the hydrophobic membrane core. PG-1 was anchored to the membrane by strong electrostatic binding of the protonated N-terminus of the peptide to the lipid head group phosphate anions. The orientation of the peptide in the membrane, and its influence on bilayer structural and dynamic properties are in excellent agreement with solid state NMR measurements [S. Yamaguchi, T. Hong, A. Waring, R.I. Lehrer, M. Hong, Solid-State NMR Investigations of Peptide-Lipid interaction and Orientation of a b-Sheet Antimicrobial Peptide, Protegrin, Biochemistry, 41 (2002) 9852-9862]. Importantly, two simulations which started from different initial orientations of the peptide converged to the same final equilibrium orientation of the peptide relative to the bilayer. The kick-shaped conformation was observed only in one of the two simulations. (c) 2006 Elsevier B.V. All rights reserved.