Characterization and Prediction of Viral Capsid Geometries

病毒衣壳几何形状的表征和预测

• 批准号: 1951678
• 负责人: Antoni Luque
• 金额: $ 30万
• 依托单位: San Diego State University Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1951678&HistoricalAwards=false
• 关键词: Characterization; Prediction; Viral; Capsid; Geometries

Viruses are the most abundant biological entity on the planet and play a crucial role in the evolution of organisms and the biogeochemistry of Earth. Closely related viruses, however, can have very dissimilar genomes, complicating integration of knowledge acquired from the study of independent viruses, and limiting prediction of the characteristics and potential threats of emerging viruses. Viruses, however, conserve a few structural properties that could help circumvent this problem. Most viruses store their infective genetic material in a protein shell called a capsid. The capsid self-assembles from multiple copies of the same (or similar) proteins, and most capsids display icosahedral symmetry. This architecture optimizes the interaction of proteins and the volume available to store the viral genetic information. This research project hypothesizes that viruses have evolved a limited set of replication strategies to specialize and exploit the reduced number of geometrical templates capable of forming icosahedral capsids. This, in turn, may have constrained the number of three-dimensional configurations adopted by capsid proteins, providing a mechanistic rationale for the existence of viral structural lineages. This hypothesis will be tested by analyzing and comparing hundreds of viruses from multiple different viral families using novel mathematical methods. Confirming this hypothesis will offer a quantitative framework to study viral evolution and open the door to design of generic antiviral strategies targeting viruses in the same structural lineage.Only ten protein folds have been identified among major capsid proteins of viruses that form icosahedral capsids. These folds define viral lineages that group viruses that can be genetically unrelated and infect hosts from different domains of life. This limited number of folds contrasts with the vast genetic diversity of viruses. The existence of these folds across the virosphere, however, remains unknown. Here, it is hypothesized that there is a direct relationship between the viral replication strategy of each viral lineage, the icosahedral lattice of the capsid, and the fold of capsid proteins. The hypothesis will be tested by developing a database that will include the viral replication, protein fold, and capsid lattice of five hundred viruses that have been reconstructed at high or medium molecular resolution. Voronoi tessellations and protein-protein interaction lattices will be obtained to identify computationally the icosahedral lattice associated to each virus. Additionally, molecular measurements of the reconstructed capsids will be obtained to establish allometric relationships for at least one viral lineage, facilitating the prediction of icosahedral capsid properties from genomic information. The new icosahedral framework will be also extended to obtain new sets of elongated capsids, which represent the second most abundant type of capsid. The methods will be disseminated online for use by viral structure researchers.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

病毒是地球上最丰富的生物实体，在生物进化和地球生物地球化学中起着至关重要的作用。然而，密切相关的病毒可能具有非常不同的基因组，使从独立病毒研究中获得的知识的整合变得复杂，并限制了对新出现病毒的特征和潜在威胁的预测。然而，病毒保留了一些结构特性，可以帮助规避这个问题。大多数病毒将其传染性遗传物质储存在一种叫做衣壳的蛋白质外壳中。衣壳由相同（或相似）蛋白质的多个拷贝自组装，并且大多数衣壳显示二十面体对称。这种结构优化了蛋白质的相互作用和存储病毒遗传信息的可用体积。该研究项目假设病毒已经进化出一套有限的复制策略，以专门利用能够形成二十面体衣壳的减少的几何模板数量。反过来，这可能限制了衣壳蛋白采用的三维构型的数量，为病毒结构谱系的存在提供了机制基础。这一假设将通过使用新颖的数学方法分析和比较来自多个不同病毒家族的数百种病毒来验证。证实这一假设将为研究病毒进化提供一个定量框架，并为设计针对相同结构谱系的病毒的通用抗病毒策略打开大门。在形成二十面体衣壳的病毒的主要衣壳蛋白中，仅鉴定出10个蛋白质折叠。这些褶皱定义了病毒谱系，将基因不相关的病毒分组，感染来自不同生命领域的宿主。这种有限数量的折叠与病毒巨大的遗传多样性形成鲜明对比。然而，在整个病毒圈中是否存在这些褶皱仍然未知。在这里，假设在每个病毒谱系的病毒复制策略、衣壳的二十面体晶格和衣壳蛋白的折叠之间存在直接关系。该假设将通过建立一个数据库来验证，该数据库将包括500种病毒的病毒复制、蛋白质折叠和衣壳晶格，这些病毒已在高或中等分子分辨率下重建。将获得Voronoi镶嵌和蛋白质-蛋白质相互作用晶格，以计算识别与每种病毒相关的二十面体晶格。此外，将获得重建衣壳的分子测量，以建立至少一种病毒谱系的异速生长关系，促进从基因组信息预测二十面体衣壳特性。新的二十面体框架也将被扩展以获得新的细长衣壳，这代表了第二丰富的衣壳类型。这些方法将在网上发布，供病毒结构研究人员使用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

2D and 3D coral models imaged in Curaçao: George, Mullinix, et al PeerJ 2021

库拉索岛拍摄的 2D 和 3D 珊瑚模型：George、Mullinix 等人 PeerJ 2021

• DOI: 10.5061/dryad.5x69p8d2x
• 发表时间: 2021
• 期刊: Dryad
• 作者: George, Emma E.;Mullinix, James A.;Meng, Fanwei;Bailey, Barbara A.;Edwards, Clinton;Felts, Ben;Haas, Andreas F.;Hartmann, Aaron;Mueller, Benjamin;Roach, Ty F.
• 通讯作者: Roach, Ty F.

Empirical and Theoretical Analysis of Particle Diffusion in Mucus

• DOI: 10.3389/fphy.2021.594306
• 发表时间: 2021-11-23
• 期刊: FRONTIERS IN PHYSICS
• 影响因子: 3.1
• 作者: Cobarrubia, Antonio;Tall, Jarod;Luque, Antoni
• 通讯作者: Luque, Antoni