基于分子动力学模拟研究pH对抗菌肽LL-37结构的影响  

The effect of p H value on the conformational characteristics of the antimicrobial peptide LL-37 studied by molecular dynamics simulations

作　　者：彭冉[1,2] 赵立岭[1] 曹赞霞[1] 王吉华[1] 

机构地区：[1]山东省功能大分子生物物理重点实验室德州学院物理与电子信息学院,德州253023 [2]山东师范大学物理与电子科学学院,济南250014

出　　处：《中国抗生素杂志》2015年第4期245-250,277,共7页Chinese Journal of Antibiotics

基　　金：国家自然科学基金(No.61271378;No.31000324和No.30970561);山东自然科学基金(No.ZR2014AL014)

摘　　要：目的研究溶液p H变化对抗菌肽LL-37结构的影响。方法利用分子动力学模拟方法,采用GROMACS软件包和OPLS-AA力场,分别在中性和强碱性条件下对LL-37进行模拟,总模拟时间达1微秒,最后对模拟轨迹进行分析处理。结果LL-37在中性环境下具有部分螺旋结构存在,特别是N端部分残基,结构具有较大柔性;在强碱性环境下,螺旋含量增多,抗菌核心区域残基形成螺旋结构的几率明显增大,结构稳定性增强。结论 p H值的增大会促进LL-37螺旋结构的形成,螺旋结构的形成和与膜结合是协同的。N端残基易形成螺旋,然后是抗菌核心区域。LL-37在中性环境下的结构特征与其行使多功能的角色相一致。该研究首次分析了LL-37在中性环境下的结构特征及p H的影响,有助于认识其抗菌机制及新药设计。Objective To study the effect of solution pH on structure characteristics of antibacterial peptide LL-37. Methods Based on molecular dynamics simulations, LL-37 had been simulated with GROMACS software package, OPLS-AA force field and TIP4P water model under neutral solution and strong alkaline solution, respectively. The simulation time was up to 1 microsecond and the simulation trajectories were analyzed. The conformational characteristics were pictured by the probability of secondary structure formation, root mean square fluctuation of atoms and contact between residues. Results LL-37, especially its N-terminal residues of LL-37 formed helical structures under neutral environment, and the structures had high flexibility. Under strong alkaline condition, the helical content increased and the possibility for residues located at antibacterial core region to form helical structure was significantly increased. At the same time, the structure stability was also enhanced. Conclusion For LL-37, the increase of pH value can promote the formation of LL-37 helical structure. The formation of LL- 37 helical structure and membrane binding is collaborative. The residues located at N terminal are more prone to form a helical structure than others and followed by the residues located at antibacterial core region. The structure characteristics of LL-37 under neutral solution are consistent with its multifunctional role. This work discusses the structure characteristics in neutral environment and the effect of pH value on structure of LL-37, which is important for understanding the antimicrobial mechanism of LL-37 and new drug design.

关 键 词：分子动力学模拟 抗菌肽 LL-37 α-螺旋结构 

分 类 号：Q617[生物学—生物物理学] Q51