Multiscale Macromolecular Assembly Pathways via Algebraic Combinatorics

通过代数组合的多尺度大分子组装途径

• 批准号: 0714912
• 负责人: Meera Sitharam
• 金额: $ 54.87万
• 依托单位: University of Florida
• 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: 2007-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0714912&HistoricalAwards=false
• 关键词: Multiscale; Macromolecular; Assembly; Pathways; via

Icosahedral viral shell assembly starting from identical protein monomers is an outstanding but poorly understood example of symmetric macromolecularself-assembly occuring in nature. We propose to develop and biochemically validate a novel multiscale mathematical and computational model and associatedsoftware tools to answer focused questions about viral shell assembly pathways. The proposed approach is based on 3 novel ingredients. (i) Formalization of carefully focused questions about the structureof assembly pathways, which depend only on static geometric and symmetry constraints. Avoidance of dynamics facilitates computational tractability and an intuitive theory of pathway structure.(ii) Development of a modular, two-scale virus assembly model that makes the mathematics transparent and leads to new directions in geometric complexity and algebraic combinatorics.(iii)Independent biochemical validation of the 2 separate scales of the model, using known data as well as new experiments.An array of applications in nanoscience and engineering, biosensor and gene therapy follow from effective models of symmetric macromolecular assembly pathways. Such models would additionally help arrest viral self-assembly and hence numerous plant and animal diseases. Opensource software built atop the PI's FRONTIER geometric constraint solving opensource software suite, and benchmark virus data will be developed for prediction and visualization of self-assembly pathways and for rigorous comparisons. The grant will foster a closely interacting, interdisciplinary group of students and will expose each of them to research in mathematics, structural biology, theoretical computer science, algorithms and software development. Outreach is planned via an interdisciplinary workshop at DIMACS or at IMA and in university press releases.

从相同的蛋白质单体开始的二十面体病毒壳组装是一个出色但知之甚少的例子，是自然界中发生的对称大分子自我组装的例子。我们建议开发和生化验证一种新型的多尺度数学和计算模型以及相关软件工具，以回答有关病毒外壳组装途径的重点问题。提出的方法基于3种新成分。 （i）关于组装途径结构的精心集中的问题的形式化，该问题仅取决于静态几何和对称性约束。避免动力学的避免促进计算障碍和途径结构的直觉理论。（ii）开发模块化的两尺度病毒装配模型，该模型使数学透明，并导致几何复杂性和代数组合中的新方向。纳米科学和工程，生物传感器和基因疗法遵循的对称大分子组装途径的有效模型。这样的模型还将有助于阻止病毒自我组装，从而使许多动植物疾病。 OpenSource软件在PI的前沿几何约束求解OpenSource软件套件上构建，并且将开发基准病毒数据，以预测和可视化自组装途径和严格的比较。该赠款将促进一个紧密的互动，跨学科的学生小组，并将每个人都暴露于数学，结构生物学，理论计算机科学，算法和软件开发方面的研究。外展计划是通过DIMAC或IMA和大学新闻稿的跨学科研讨会计划的。