Paine Amelia W, Hagan Michael F, Manoharan Vinothan N
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, United States.
Martin Fisher School of Physics, Brandeis University, Waltham, Massachusetts 02453, United States.
J Phys Chem B. 2025 Feb 6;129(5):1516-1528. doi: 10.1021/acs.jpcb.4c07215. Epub 2025 Jan 22.
In many simple viruses and virus-like particles, the protein capsid self-assembles around a nucleic-acid genome. Although the assembly process has been studied in detail, relatively little is known about how the capsid disassembles, a potentially important step for infection (in viruses) or cargo delivery (in virus-like particles). We investigate capsid disassembly using a coarse-grained molecular dynamics model of a = 1 dodecahedral capsid and an RNA-like polymer. We alter the interactions between the subunits of the capsid as well as the ionic strength of the solution to induce partial or complete disassembly of self-assembled particles. We find that disassembly follows nucleation-and-growth kinetics, where the nucleation barrier is related to the interaction strengths as well as to the conformation of the polymer. In particular, we find that polymer segments that interact with adjacent subunits reinforce the subunit-subunit contacts. These results have implications for the design of virus-like particles for applications such as drug delivery. A cargo designed with reinforcement in mind might be used to control the stability of such particles and mediate disassembly.
在许多简单病毒和病毒样颗粒中,蛋白质衣壳围绕核酸基因组进行自我组装。尽管对组装过程已进行了详细研究,但对于衣壳如何解体却知之甚少,而这一步骤对于感染(在病毒中)或货物递送(在病毒样颗粒中)可能至关重要。我们使用一种由12面体衣壳和类RNA聚合物组成的粗粒度分子动力学模型来研究衣壳解体。我们改变衣壳亚基之间的相互作用以及溶液的离子强度,以诱导自组装颗粒的部分或完全解体。我们发现解体遵循成核-生长动力学,其中成核屏障与相互作用强度以及聚合物的构象有关。特别地,我们发现与相邻亚基相互作用的聚合物链段会加强亚基-亚基之间的接触。这些结果对用于药物递送等应用的病毒样颗粒的设计具有启示意义。考虑到增强作用而设计的货物可用于控制此类颗粒的稳定性并介导解体。