Physics of Viral Structure and Assembly

技术概述该奖项支持关于病毒衣壳结构变化的理论研究和教育。病毒壳在材料研究中得到了应用，它们被用作纳米容器，具有稳定的表面结构，可以通过基因改变。最近对病毒外壳的生物物理研究表明，病毒外壳也可以被视为分子机器，它们采用一系列不同的结构作为其自然成熟过程的一部分。不同外壳结构之间的变化要么是通过数百种衣壳蛋白连续的、协同的构象变化，要么是通过一系列精心控制的化学反应来响应溶液条件或内部压力的变化。这个项目的主要目标是开发基于坚实的理论物理的简单的分析和数值方法，这些方法可以用来描述这些协同的结构变化和化学反应，并特别应用于噬菌体病毒Hong Kong-Hong Kong 97或HK97的情况。在成熟的过程中，HK97的蛋白质外壳从一个脆弱的蛋白质组装演变为一系列共价连接的蛋白质结构域。从事HK97研究的实验者提出了一系列的想法，例如作为组装过程中的错误纠正机制的六角对称破缺，作为将化学反应转化为大规模结构变化和产生功的机制的热布朗棘轮，以及作为影响结构变化的蛋白质基团的合作移动性机制。绩效指标旨在从物理角度开发和评估这些想法。他们将应用已经开发的方法来描述集体构象变化，特别是金兹堡-朗道相变理论。PIS将为HK97构象转变序列开发一个单一的Ginzburg-Landau描述，该描述可扩展到其他病毒外壳，并提供病毒成熟的概念统一。这些方法可以为对生物物理问题感兴趣的年轻物理学家提供新的理论工具和培训。致力于病毒材料应用的材料科学家将获得理论方法和数值模型，用于研究由活性衣壳蛋白(如HK97亚基)组成的病毒外壳，这些外壳可以进行构象和化学变化的受控程序。非技术概述该奖项支持旨在了解病毒周围蛋白质外壳结构的理论研究。在生命科学领域之外，科学家们已经发现了病毒蛋白外壳的许多实际用途。它们被用作分子规模的材料组装的支撑结构，这些材料可以通过定向组装来“设计”。大分子大小的微小金属线、太阳能电池、电池和燃料电池都是用病毒壳组装而成的。在这些应用中，壳蛋白扮演着被动的“支持”角色。新一代病毒外壳的应用将基于病毒外壳中发生的精心协调的集体物理和化学变化，逐步加强病毒外壳。PIS旨在根据对最好的研究案例--香港97病毒--的分析，制定对这种成熟过程的一般描述。这一描述可作为设计病毒壳的新应用的指南。

Technical SummaryThis award supports theoretical research and education on the structural transformations that occur in viral capsid shells. Viral shells have found applications in materials research where they are used as nanocontainers with a stable surface structure that can be genetically altered. Recent biophysical studies of viral shells have shown that viral shells can also be viewed as molecular machines that adopt a range of different structures as part of their natural maturation process. The changes between different shell structures are effected either by successive, cooperative conformational changes of hundreds of capsid proteins or by a sequence of carefully controlled chemical reactions in response to changes in solution conditions or internal pressure. The main objective of this project is to develop simple analytical and numerical methods firmly based on theoretical physics that can be used to describe these cooperative structural changes and chemical reactions and to apply them in particular to the case of the bacteriophage virus Hong-Kong 97, or HK97. During maturation the protein shell of HK97 evolves from a fragile protein assembly to a chainmail of covalently linked protein domains. Experimentalists working on HK97 have proposed a range of ideas, such as hexon symmetry breaking as an error correction mechanism during assembly, thermal Brownian ratchets as a mechanism for translating chemical reactions into large-scale structural changes and for generating work, and cooperative mobility of groups of proteins as a mechanism for effecting structural change. The PIs aim to develop and evaluate these ideas from a physical perspective. They will apply methods that have been developed to describe collective conformational changes, specifically the Ginzburg-Landau theory of phase transitions. The PIs will develop a single Ginzburg-Landau description for the sequence of HK97conformational transitions that could be extended to other viral shells and provide conceptual unity of viral maturation. These methods could provide new theoretical tools and training to young physical scientists interested in working on problems in biological physics. Materials scientists working on virus-based materials applications would be provided with theoretical methods and numerical models for studies of viral shells assembled from active capsid proteins, such as HK97 subunits, that can carry out a controlled program of conformational and chemical change.Non-Technical SummaryThis award supports theoretical research that aims to understand the structure of the protein shells that surround viruses. Scientists have found numerous practical uses for virus protein shells outside the Life Sciences. They are used as support structures for the molecular scale assembly of materials that can be "designed" by directed assembly. Tiny metallic wires, solar cells, batteries, and fuel cells that have dimensions on the scale of large molecules have all been assembled from viral shells. In these applications, the shell proteins play a passive "support" role. A new generation of applications of viral shells will be based on the exquisitely coordinated collective physical and chemical transformations that take place in viral shells, progressively strengthening it. The PIs aim to develop a general description of this maturation process based on the analysis of the best studied case: the Hong-Kong97 virus. This description may act as a guide in the design of new applications of viral shells.