Khandelia Himanshu, Kaznessis Yiannis N
Department of Chemical Engineering and Materials Science and The Digital Technology Center, University of Minnesota, 421, Washington Avenue SE Minneapolis, Minnesota 55455, USA.
J Phys Chem B. 2007 Jan 11;111(1):242-50. doi: 10.1021/jp064776j.
We implemented molecular dynamics simulations of the 13-residue antimicrobial peptide indolicidin (ILPWKWPWWPWRR-NH2) in dodecylphosphocholine (DPC) and sodium dodecyl sulfate (SDS) micelles. In DPC, a persistent cation-pi interaction between TRP11 and ARG13 defined the structure of the peptide near the interface. A transient cation-pi interaction was also observed between TRP4 and the choline group on DPC lipids. We also implemented simulation of a mutant of indolicidin in the DPC micelle where TRP11 was replaced by ALA11. As a result of the mutation, the boat-shaped conformation is lost and the structure becomes significantly less defined. On the basis of this evidence, we argue that cation-pi interactions determine the experimentally measured, well-defined boat-shaped structure of indolicidin. In SDS, the lack of such interactions and the electrostatic binding of the terminal arginine residues to the sulfate groups leads to an extended peptide structure. To the best of our knowledge, this is the first time that a cation-pi interaction between peptide side chains has been shown to stabilize the structure of a small antimicrobial peptide. The simulations are in excellent agreement with available experimental measurements: the backbone of the peptide is more ordered in DPC than in SDS; the tryptophan side chains pack against the backbone in DPC and point away from the backbone in SDS; the rms fluctuation of the peptide backbone and peptide side chains is greater in SDS than in DPC; and the peptide backbone order parameters are higher in DPC than in SDS.
我们对由13个残基组成的抗菌肽吲哚杀菌素（ILPWKWPWWPWRR-NH2）在十二烷基磷酸胆碱（DPC）和十二烷基硫酸钠（SDS）胶束中进行了分子动力学模拟。在DPC中，色氨酸11（TRP11）和精氨酸13（ARG13）之间持续存在的阳离子-π相互作用决定了肽在界面附近的结构。在TRP4和DPC脂质上的胆碱基团之间也观察到了瞬时阳离子-π相互作用。我们还对DPC胶束中色氨酸11被丙氨酸11（ALA11）取代的吲哚杀菌素突变体进行了模拟。由于这种突变，船形构象丧失，结构变得明显更不明确。基于这些证据，我们认为阳离子-π相互作用决定了实验测量的、明确的吲哚杀菌素船形结构。在SDS中，由于缺乏这种相互作用以及末端精氨酸残基与硫酸根基团的静电结合，导致肽结构伸展。据我们所知，这是首次表明肽侧链之间的阳离子-π相互作用能够稳定一种小抗菌肽的结构。模拟结果与现有的实验测量结果非常吻合：肽的主链在DPC中比在SDS中更有序；色氨酸侧链在DPC中靠向主链，而在SDS中远离主链；肽主链和肽侧链的均方根波动在SDS中比在DPC中更大；并且肽主链的序参数在DPC中比在SDS中更高。
