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病毒样颗粒(virus-like particle,VLP)是衣壳粒蛋白(Capsomere,Cap)形成的分子自组装体,在疫苗、基因治疗和药物输送等领域具有广阔应用前景。Cap的构象稳定性是影响VLP自组装的关键因素。因此,通过全原子分子动力学模拟考察溶液条件对Cap稳定性的影响,展示此过程的构象变化,分析溶剂结构等影响因素,确定溶液条件调控Cap稳定性的微观机理。模拟结果表明,在纯水和稳定缓冲液两种溶液中,蛋白质均通过静电相互作用吸引Na+富集于表面,使其和水分子共同形成包裹蛋白质的壳层结构。这是溶液稳定Cap的重要因素。稳定缓冲液中,大量Na+富集于蛋白质表面,并通过静电吸引诱导形成Cl-壳层。多壳层结构能够更好包裹蛋白质使Cap内部氢键作用增强,从而更好稳定Cap。研究结果初步展示溶液条件调控Cap稳定性的微观机理,为VLP自组装过程调控奠定理论基础。
Virus-like particle (VLP) is a molecular self-assembly formed by capsid protein (Capsomere, Cap) and has broad application prospects in the fields of vaccine, gene therapy and drug delivery. The conformational stability of Cap is a key factor that affects VLP self-assembly. Therefore, all-atom molecular dynamics simulations were used to investigate the effect of solution conditions on the stability of Cap, to show the conformational changes of the process, to analyze the influencing factors such as the solvent structure, and to determine the microscopic mechanism of solution stability on the Cap stability. The simulation results show that in the two solutions of pure water and stable buffer, the proteins attract Na + to the surface through electrostatic interaction, and form the shell structure of the protein with the water molecules. This is an important factor for the solution to stabilize Cap. In the stabilization buffer, a large amount of Na + is enriched in the protein surface and is induced to form a Cl-shell by electrostatic attraction. Multi-shelled structures can better encapsulate proteins to enhance Cap hydrogen bonds within Caps for better Cap stability. The results preliminarily demonstrated the microscopic mechanism of solution stability and stability of Cap, which laid the theoretical foundation for the regulation of VLP self-assembly process.