CAREER: Physics of Virus Structure: Energetics and Dynamics

职业：病毒结构物理学：能量学和动力学

• 批准号: 0645668
• 负责人: Roya Zandi
• 金额: $ 40万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-15 至 2014-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0645668&HistoricalAwards=false
• 关键词: CAREER; Physics; Virus; Structure; Energetics

TECHNICAL SUMMARY:This is a CAREER award supports theoretical research and education at the interface of condensed matter physics and biology. The aim of the proposed research is to set up a statistical mechanical investigation of viral structure focusing on the right (coarse-grained) level of description to capture the essential physics, yet include sufficient biochemical details to develop verifiable models to elucidate viral assembly. In particular, the following major questions will be investigated: (i) What are the relevant thermodynamic control parameters that determine the size and shape of empty capsids? (ii) What is the effect of the enclosed genome on the size and shape of capsid, in particular for the case of co-assembly (where genome triggers the formation process)? And (iii) what are the effects of all these factors on the kinetics of self-assembly? Important issues in the assembly of empty capsids are the relation between protein shape, hydrophobic and screened-coulomb interactions between them, and the geometry of the icosahedral, cylindrical and conical assemblies. The research will focus on the statistical mechanics of viral self-assembly, both equilibrium and nonequilibrium. Since capsid assembly is akin to a thermodynamic phase transition, nucleation theory will be used for the kinetics. Furthermore, to elucidate the simplest physical role played by an encapsidated chain in determining the preferred size of a virus, the self-consistent field theory of polyelectrolyte adsorption will be extended to confined geometries. Of interest is how the free energy of viral particles is influenced by genome length and the strength of genome/capsid attractive interaction. In view of the complexity of the physics, the analytical theory is to be augmented by scaling methods, numerical investigations, and computer simulation. In particular, the PI will perform a series of Monte Carlo and Brownian dynamics computer simulations to explore the equilibrium and kinetic aspects of viral self-assembly. Our simulations involve a system of model capsid proteins for investigating the selection of shell size and symmetry among capsids.This award also contributes to the education of undergraduate, graduate and postgraduate students, and particularly to the training of the next generation of condensed matter and biological physicists. An outreach program for K-12 level teachers in the Riverside and San Bernardino counties, and workshops for women aim to improve participation of underrepresented groups in science. NON-TECHNICAL SUMMARY:This is a CAREER award supports theoretical research and education at the interface of condensed matter physics and biology. A fundamental step in the replication of a viral particle is the self-assembly of its rigid shell (capsid) from its constituent proteins and enclosed genome. The physics of viruses is exceptionally rich. It involves understanding the behavior of large molecules (polymers) in confined volumes and the co-operative growth of genomes and capsids. While the in vitro and in vivo assemblies of viruses are considered as the paradigm for self-assembly in biology, the physical principles that underlie virus structure are only beginning to be understood. The PI will carry out theoretical research using the tools of statistical physics to attack important problems aimed at improving our understanding of virus structure and assembly.Since capsids play a vital role in genome replication and intercellular movement of viruses, understanding viral assembly may be critical in the development of new anti-viral therapies and systematic treatment of viral infection. This research also connects with emerging areas of materials science - the synthesis of viral nano-containers for enclosing non-genetic material and designing novel biomimetic materials. Further, as viruses infect all kinds of hosts (bacteria, plants, and animals) with various degrees of severity (from the common cold to AIDS), there is keen interest among students at all levels to understand the mechanisms governing viral life cycle.This award also contributes to the education of undergraduate, graduate and postgraduate students, and particularly to the training of the next generation of condensed matter and biological physicists. An outreach program for K-12 level teachers in the Riverside and San Bernardino counties, and workshops for women aim to improve participation of underrepresented groups in science.

技术摘要：这是一项职业奖，支持凝聚态物理和生物学领域的理论研究和教育。拟议研究的目的是建立病毒结构的统计机械研究，重点关注正确（粗粒度）的描述水平，以捕获基本物理原理，同时包括足够的生化细节，以开发可验证的模型来阐明病毒组装。特别是，将研究以下主要问题：（i）决定空衣壳大小和形状的相关热力学控制参数是什么？ (ii) 封闭的基因组对衣壳的大小和形状有什么影响，特别是在共组装的情况下（基因组触发形成过程）？ (iii) 所有这些因素对自组装动力学有何影响？空衣壳组装中的重要问题是蛋白质形状、它们之间的疏水性和屏蔽库仑相互作用之间的关系，以及二十面体、圆柱形和圆锥形组装体的几何形状。该研究将重点关注病毒自组装的统计机制，包括平衡和非平衡。由于衣壳组装类似于热力学相变，因此成核理论将用于动力学。此外，为了阐明衣壳链在确定病毒的首选大小方面所发挥的最简单的物理作用，聚电解质吸附的自洽场论将扩展到受限的几何形状。有趣的是病毒颗粒的自由能如何受到基因组长度和基因组/衣壳吸引力相互作用强度的影响。鉴于物理学的复杂性，分析理论将通过标度方法、数值研究和计算机模拟来增强。特别是，PI 将进行一系列蒙特卡罗和布朗动力学计算机模拟，以探索病毒自组装的平衡和动力学方面。我们的模拟涉及一个衣壳蛋白模型系统，用于研究衣壳尺寸和对称性的选择。该奖项还有助于本科生、研究生和研究生的教育，特别是对下一代凝聚态物理学家和生物物理学家的培训。针对河滨县和圣贝纳迪诺县的 K-12 年级教师的外展计划以及针对女性的讲习班旨在提高代表性不足的群体对科学的参与。非技术摘要：这是一个职业奖，支持凝聚态物理和生物学领域的理论研究和教育。病毒颗粒复制的一个基本步骤是由其组成蛋白和封闭的基因组自组装其刚性外壳（衣壳）。病毒的物理学非常丰富。它涉及了解大分子（聚合物）在有限体积内的行为以及基因组和衣壳的协同生长。虽然病毒的体外和体内组装被认为是生物学中自组装的范例，但病毒结构背后的物理原理才刚刚开始被理解。 PI将利用统计物理学工具开展理论研究，解决重要问题，旨在提高我们对病毒结构和组装的理解。由于衣壳在病毒的基因组复制和细胞间运动中发挥着至关重要的作用，了解病毒组装对于开发新的抗病毒疗法和病毒感染的系统治疗可能至关重要。这项研究还与材料科学的新兴领域相联系——用于封装非遗传材料的病毒纳米容器的合成和设计新型仿生材料。此外，由于病毒以不同程度的严重程度（从普通感冒到艾滋病）感染各种宿主（细菌、植物和动物），各个级别的学生都对了解控制病毒生命周期的机制产生了浓厚的兴趣。该奖项还有助于本科生、研究生和研究生的教育，特别是对下一代凝聚态物理学家和生物物理学家的培养。针对河滨县和圣贝纳迪诺县的 K-12 年级教师的外展计划以及针对女性的讲习班旨在提高代表性不足的群体对科学的参与。