ERI: Modeling Bacterial Microcompartment Assembly Using a Data-Driven Multiscale Framework

ERI：使用数据驱动的多尺度框架对细菌微区室组装进行建模

• 批准号: 2138620
• 负责人: Alexander Pak
• 金额: $ 20万
• 依托单位: Colorado School of Mines
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2138620&HistoricalAwards=false
• 关键词: ERI; Modeling; Bacterial; Microcompartment; Assembly

The scope of industrial usage of microbes is increasing. Production of fuels, chemicals, and vaccines are just a few of the most recent applications. Some products cannot be made by microbes because of the toxicity of intermediate compounds. This project is focused on one solution to the toxicity problem, confining the toxic reactions to a separate compartment inside the cell. The focus of this project is on bacterial microcompartments that occur naturally. The goal is to identify the organizing principles that control their size, shape, and composition. Research outcomes will be adapted into hands-on learning modules to expose undergraduates and underrepresented groups at nearby high schools to integrated aspects of biology, physics, data science, engineering, and computer modeling.This project will investigate the Haliangium ochraceum microcompartment. This model system was recently characterized with high- resolution structural information. Essential protein interactions that regulate the assembly of the microcompartment shells will be investigated by deriving computational models using systematic dimensional reduction techniques. The research plan includes two main objectives: (1) To quantify free energy landscapes for protein oligomerization and (2) To classify molecular determinants that control microcompartment morphology using coarse-grained assembly simulations. The computational framework will leverage systematic multiscale algorithms as hypothesis testing tools. This should provide a novel perspective on the relationship between microscopic and macroscopic protein assembly behavior.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.

微生物的工业使用范围正在增加。燃料，化学物质和疫苗的生产只是最新应用中的一些。由于中间化合物的毒性，某些产品无法由微生物制成。该项目集中在一种解决毒性问题的解决方案上，将毒性反应限制在细胞内部的一个单独的隔间中。该项目的重点是自然发生的细菌微校区。 目的是确定控制其大小，形状和组成的组织原理。研究成果将适应动手学习模块，以揭示附近高中的本科生和代表性不足的群体，以使生物学，物理学，数据科学，工程和计算机建模的综合方面进行研究。该模型系统最近以高分辨率结构信息进行了表征。通过使用系统的尺寸还原技术得出计算模型，研究了调节微型壳壳组装的必需蛋白质相互作用。研究计划包括两个主要目标：（1）量化蛋白质寡聚化的自由能景观和（2），以使用粗粒装配模拟来控制微校区形态的分子决定因素。计算框架将利用系统的多尺度算法作为假设测试工具。这应该为微观和宏观蛋白质组装行为之间的关系提供一个新的观点。该奖项反映了NSF的法定任务，并且使用基金会的知识分子优点和更广泛的影响评估标准，被认为值得通过评估来获得支持。

项目成果

Formalizing Coarse-Grained Representations of Anisotropic Interactions at Multimeric Protein Interfaces Using Virtual Sites

• DOI: 10.1021/acs.jpcb.3c07023
• 发表时间: 2024-02-05
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY B
• 影响因子: 3.3
• 作者: Christians，Luc F.;Halingstad，Ethan V.;Pak，Alexander J.
• 通讯作者: Pak，Alexander J.