{"title":"病毒核苷酸从无序到有序转变过程中的玻璃样弛豫动力学","authors":"Guillaume Tresset, Siyu Li, Laetitia Gargowitsch, Lauren Matthews, Javier Pérez, Roya Zandi","doi":"10.1021/acs.jpclett.4c02158","DOIUrl":null,"url":null,"abstract":"<p><p>Nucleocapsid self-assembly is an essential yet elusive step in virus replication. Using time-resolved small-angle X-ray scattering on a model icosahedral ssRNA virus, we reveal a previously unreported kinetic pathway. Initially, RNA-bound capsid subunits rapidly accumulate beyond the stoichiometry of native virions. This is followed by a disorder-to-order transition characterized by glass-like relaxation dynamics and the release of excess subunits. Our molecular dynamics simulations, employing a coarse-grained elastic model, confirm the physical feasibility of self-ordering accompanied by subunit release. The relaxation can be modeled by an exponential integral decay on the mean squared radius of gyration, with relaxation times varying within the second range depending on RNA type and subunit concentration. A nanogel model suggests that the initially disordered nucleoprotein complexes quickly reach an equilibrium size, while their mass fractal dimension continues to evolve. Understanding virus self-assembly is not only crucial for combating viral infections, but also for designing synthetic virus-inspired nanocages for drug delivery applications.</p>","PeriodicalId":62,"journal":{"name":"The Journal of Physical Chemistry Letters","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Glass-like Relaxation Dynamics during the Disorder-to-Order Transition of Viral Nucleocapsids.\",\"authors\":\"Guillaume Tresset, Siyu Li, Laetitia Gargowitsch, Lauren Matthews, Javier Pérez, Roya Zandi\",\"doi\":\"10.1021/acs.jpclett.4c02158\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Nucleocapsid self-assembly is an essential yet elusive step in virus replication. Using time-resolved small-angle X-ray scattering on a model icosahedral ssRNA virus, we reveal a previously unreported kinetic pathway. Initially, RNA-bound capsid subunits rapidly accumulate beyond the stoichiometry of native virions. This is followed by a disorder-to-order transition characterized by glass-like relaxation dynamics and the release of excess subunits. Our molecular dynamics simulations, employing a coarse-grained elastic model, confirm the physical feasibility of self-ordering accompanied by subunit release. The relaxation can be modeled by an exponential integral decay on the mean squared radius of gyration, with relaxation times varying within the second range depending on RNA type and subunit concentration. A nanogel model suggests that the initially disordered nucleoprotein complexes quickly reach an equilibrium size, while their mass fractal dimension continues to evolve. Understanding virus self-assembly is not only crucial for combating viral infections, but also for designing synthetic virus-inspired nanocages for drug delivery applications.</p>\",\"PeriodicalId\":62,\"journal\":{\"name\":\"The Journal of Physical Chemistry Letters\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Physical Chemistry Letters\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.jpclett.4c02158\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Physical Chemistry Letters","FirstCategoryId":"1","ListUrlMain":"https://doi.org/10.1021/acs.jpclett.4c02158","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/2 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
摘要
核壳自组装是病毒复制过程中必不可少但又难以捉摸的一步。通过对一种二十面体 ssRNA 病毒模型进行时间分辨小角 X 射线散射,我们揭示了一种以前从未报道过的动力学途径。最初,与 RNA 结合的囊膜亚基迅速积累,超过了原生病毒的化学计量。随后是无序到有序的转变,其特点是玻璃样弛豫动力学和过剩亚基的释放。我们采用粗粒度弹性模型进行分子动力学模拟,证实了自有序化伴随亚基释放的物理可行性。弛豫可以用平均回转半径平方的指数积分衰减来模拟,弛豫时间在秒范围内变化,取决于 RNA 类型和亚基浓度。纳米凝胶模型表明,最初无序的核蛋白复合物很快就会达到平衡尺寸,而其质量分形维度则会继续演变。了解病毒的自组装不仅对抗击病毒感染至关重要,而且对设计用于药物输送的合成病毒启发纳米载体也至关重要。
Glass-like Relaxation Dynamics during the Disorder-to-Order Transition of Viral Nucleocapsids.
Nucleocapsid self-assembly is an essential yet elusive step in virus replication. Using time-resolved small-angle X-ray scattering on a model icosahedral ssRNA virus, we reveal a previously unreported kinetic pathway. Initially, RNA-bound capsid subunits rapidly accumulate beyond the stoichiometry of native virions. This is followed by a disorder-to-order transition characterized by glass-like relaxation dynamics and the release of excess subunits. Our molecular dynamics simulations, employing a coarse-grained elastic model, confirm the physical feasibility of self-ordering accompanied by subunit release. The relaxation can be modeled by an exponential integral decay on the mean squared radius of gyration, with relaxation times varying within the second range depending on RNA type and subunit concentration. A nanogel model suggests that the initially disordered nucleoprotein complexes quickly reach an equilibrium size, while their mass fractal dimension continues to evolve. Understanding virus self-assembly is not only crucial for combating viral infections, but also for designing synthetic virus-inspired nanocages for drug delivery applications.
期刊介绍:
The Journal of Physical Chemistry (JPC) Letters is devoted to reporting new and original experimental and theoretical basic research of interest to physical chemists, biophysical chemists, chemical physicists, physicists, material scientists, and engineers. An important criterion for acceptance is that the paper reports a significant scientific advance and/or physical insight such that rapid publication is essential. Two issues of JPC Letters are published each month.