衣壳粒蛋白稳定性的分子动力学模拟

Molecular Dynamics Simulation of the Stability of Capsomere

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 particles （VLP） is a selfassembly of capsomere （Cap） with great potential in vaccinology, gene therapy, drug delivery, and materials science. The stability of Cap is crucial for its selfassembly to VLP. In the present study, the allatom molecular dynamics （MD） simulations are performed to investigate the effect of solution conditions on the stabilization of Cap. The conformational transition has been investigated. The structure of solvent is also examined to explore the molecular mechanism of the regulation on the stabilization of Cap by solution conditions. In both stabilization buffer and aqueous solution, Na＋ can be attracted and accumulated around protein through electrostatic interaction, and forms a shell with water molecules. This is very important for the stabilization of Cap. Moreover, in stabilization buffer, the shell formed by accumulated Na＋ around the protein can induce the formation of a shell of Cl-. The multishell structure causes more hydrogen bonds within Cap and consequently provides better stabilization of Cap. These results provide molecular insights into the effect of solution condition on the stabilization of Cap, which would be beneficial for the regulation of VLP selfassembly.