Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
J Phys Chem B. 2013 May 9;117(18):5411-21. doi: 10.1021/jp311170w. Epub 2013 Apr 26.
Virus-like particles (VLPs) are highly organized nanoparticles that have great potential in vaccinology, gene therapy, drug delivery, and materials science. However, the application of VLPs is hindered by obstacles in their design and production due to low efficiency of self-assembly. In the present study, all-atom (AA) molecular dynamics (MD) simulations coupled with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method are utilized to examine the molecular interactions in the capsomere of a murine polyomavirus (MPV) VLP. It is found that both low ionic strength and the intracapsomere disulfide bonds are favorable for maintaining a stable capsomere. Simulation results examining the effects of solution conditions on the stabilization of a capsomere were verified by calorimetry experiments. Simulation results of free energy decomposition indicate that hydrophobic interaction is favorable for the formation of a capsomere, whereas electrostatic interaction is unfavorable. With increasing ionic strength, the dominant interaction for the stabilization of a capsomere changes from hydrophobic to electrostatic. By comprehensive analyses, the key amino acid residues (hot spots) in VP1 protein aiding formation of a capsomere in different solution conditions have been identified. These results provide molecular insights into the stabilization of building blocks for VLP and are expected to have implications in their partitioning between the correct and off-pathway reactions in VLP assembly.
病毒样颗粒（VLPs）是高度有序的纳米颗粒，在疫苗学、基因治疗、药物输送和材料科学方面具有巨大的潜力。然而，由于自组装效率低，VLPs 的设计和生产存在障碍，限制了其应用。在本研究中，采用全原子（AA）分子动力学（MD）模拟与分子力学-泊松-玻尔兹曼表面积（MM-PBSA）方法相结合，研究了鼠多瘤病毒（MPV）VLP 衣壳的分子相互作用。结果发现，低离子强度和衣壳内的二硫键都有利于维持稳定的衣壳。通过热学法实验验证了模拟结果，考察了溶液条件对衣壳稳定的影响。自由能分解的模拟结果表明，疏水相互作用有利于衣壳的形成，而静电相互作用则不利于衣壳的形成。随着离子强度的增加，稳定衣壳的主要相互作用从疏水相互作用转变为静电相互作用。通过综合分析，确定了 VP1 蛋白中有助于在不同溶液条件下形成衣壳的关键氨基酸残基（热点）。这些结果为 VLP 构建块的稳定提供了分子见解，并有望对 VLP 组装过程中正确和错误途径反应的分配产生影响。
