Interaction mechanism of insulin with ZnO nanoparticles by replica exchange molecular dynamics simulation

The interaction of ZnO nanoparticles with biological molecules such as proteins is one of the most important and challenging problems in molecular biology. Molecular dynamics (MD) simulations are useful technique for understating the mechanism of various interactions of proteins and nanoparticles. In the present work, the interaction mechanism of insulin with ZnO nanoparticles was studied. Simulation methods including MD and replica exchange molecular dynamics (REMD) and their conditions were surveyed. According to the results obtained by REMD simulation, it was found that insulin interacts with ZnO nanoparticle surface via its polar and charged amino acids. Unfolding insulin at ZnO nanoparticle surface, the terminal parts of its chains play the main role. Due to the linkage between chain of insulin and chain of disulfide bonds, opposite directional movements of N terminal part of chain A (toward nanoparticle surface) and N termini of chain B (toward solution) make insulin unfolding. In unfolding of insulin at this condition, its helix structures convert to random coils at terminal parts chains.

氧化锌纳米颗粒（ZnO nanoparticles）与蛋白质等生物分子的相互作用，是分子生物学领域中最重要且最具挑战性的研究课题之一。分子动力学（MD）模拟是解析蛋白质与纳米颗粒各类相互作用机制的有效技术手段。本研究针对胰岛素与氧化锌纳米颗粒的相互作用机制展开了探究。本工作调研了包括分子动力学（MD）模拟及副本交换分子动力学（REMD）在内的模拟方法及其模拟条件。根据副本交换分子动力学模拟所得结果，研究发现胰岛素可通过其极性与带电氨基酸残基与氧化锌纳米颗粒表面发生相互作用。在氧化锌纳米颗粒表面发生解折叠时，胰岛素肽链的末端区域发挥了主要作用。由于胰岛素肽链与二硫键之间存在连接关系，A链的N端（朝向纳米颗粒表面）与B链的N端（朝向溶液）出现反向运动，进而引发胰岛素的解折叠。在该条件下的胰岛素解折叠过程中，其肽链末端区域的螺旋结构会转变为无规卷曲。