Nanomanufacturing of Protein Macromolecular Frameworks Through an Integrated Bioengineering and Computational Approach

通过综合生物工程和计算方法纳米制造蛋白质大分子框架

• 批准号: 1922883
• 负责人: Masaki Uchida
• 金额: $ 49.85万
• 依托单位: California State University-Fresno Foundation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1922883&HistoricalAwards=false
• 关键词: Nanomanufacturing; Protein; Macromolecular; Frameworks; Through

New materials with innovative functionalities are needed to build new and useful devices and systems that enrich our lives. Ordered three-dimensional arrays built from nanoscale building-blocks, often called superlattices, are exciting because new functionalities can emerge from the interactions between individual building-blocks. The use of proteins as building-blocks is a groundbreaking new direction because proteins exhibit a wide range of properties and behavior, including catalytic and immune activities, which are often difficult to realize in synthetic molecules. Making ordered materials by conventional protein crystallization is a laborious procedure and the ability to tailor the structure of protein crystals is limited. This award supports fundamental research to develop versatile and tunable approaches to manufacture superlattice materials constructed of proteins. The availability of these unique protein-based materials impacts diverse industries such as energy, biomedical and catalysis, which advances national welfare. This project uniquely integrates several disciplines including materials science, bioengineering and computational modeling. The integration of experimental and computational approaches in this project impacts research efforts of the Network for Computational Nanotechnology (NCN), synergistically. Alongside the scientific impact of the project, it also leverages the multi-disciplinary approach to promote students, including women and minorities, on this project by acquiring broad skills and knowledge and by providing a positive impact on science education.The research team envisions that protein cage nanoparticles and linker proteins, which bind non-covalently to symmetry-specific sites on the protein cages, are promising building-blocks for constructing a new class of protein superlattices, i.e. protein macromolecular frameworks. Protein cages have hollow spherical architectures composed of a distinct number of subunits with well-defined symmetry-specific sites. The investigators anticipate that specific binding geometries between protein cages and linkers result in highly regular network structures with a wide range of functionalities. The research team integrates bioengineering and computational modeling approaches to develop a range of linker molecules with different lengths and binding affinities to protein cages. By connecting the protein cages together through protein linkers, they are geometrically confined, thus forming highly regulated structures. The structure of the protein macromolecular frameworks is tunable through the selection of protein cages and specific linker proteins. Additionally, protein macromolecular frameworks have two types of unique spaces internally to accommodate cargo molecules. These are interior cavity of individual protein cages and interstitial space between protein cages within the lattice. The team demonstrates that various cargo molecules, such as enzymes, could be encapsulated inside of the protein cages. In this project, reversible incorporation and release of guest molecules are studied, which could lead protein macromolecular frameworks to practical applications such as drug delivery and catalysis.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.

需要具有创新功能的新材料来构建新的有用的设备和系统，以丰富我们的生活。由纳米级构建块（通常称为超晶格）构建的有序三维阵列令人兴奋，因为新的功能可以从单个构建块之间的相互作用中出现。使用蛋白质作为构建块是一个突破性的新方向，因为蛋白质表现出广泛的性质和行为，包括催化和免疫活性，这些通常难以在合成分子中实现。通过常规的蛋白质结晶制备有序材料是一个费力的过程，并且定制蛋白质晶体结构的能力有限。该奖项支持基础研究，以开发多功能和可调的方法来制造由蛋白质构成的超晶格材料。这些独特的蛋白质基材料的可用性影响了能源、生物医学和催化等不同行业，从而促进了国家福利。该项目独特地整合了材料科学、生物工程和计算建模等多个学科。该项目中实验和计算方法的整合协同影响了计算纳米技术网络（NCN）的研究工作。除了该项目的科学影响外，它还利用多学科方法，通过获得广泛的技能和知识，并通过对科学教育产生积极影响，促进包括妇女和少数民族在内的学生参与该项目。研究团队设想，蛋白质笼纳米颗粒和连接蛋白，非共价结合到蛋白质笼上的特定位点，是构建一类新的蛋白质超晶格即蛋白质大分子框架的有前途的构建块。蛋白质笼具有中空的球形结构，由不同数量的亚基组成，具有明确的蛋白质特异性位点。研究人员预计，蛋白质笼和连接体之间的特定结合几何形状导致具有广泛功能的高度规则的网络结构。该研究团队整合了生物工程和计算建模方法，开发了一系列具有不同长度和与蛋白质笼结合亲和力的连接分子。通过蛋白质接头将蛋白质笼连接在一起，它们在几何上受到限制，从而形成高度调控的结构。蛋白质大分子框架的结构是可调的，通过选择蛋白质笼和特定的接头蛋白。此外，蛋白质大分子框架内部具有两种类型的独特空间以容纳货物分子。这些是单个蛋白质笼的内腔和晶格内蛋白质笼之间的间隙空间。研究小组证明，各种货物分子，如酶，可以被封装在蛋白质笼内。该项目研究客体分子的可逆结合和释放，这可能导致蛋白质大分子框架的实际应用，如药物输送和催化。该奖项反映了NSF的法定使命，并通过使用基金会的智力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

Protein docking model evaluation by 3D deep convolutional neural networks

• DOI: 10.1093/bioinformatics/btz870
• 发表时间: 2020-04-01
• 期刊: BIOINFORMATICS
• 影响因子: 5.8
• 作者: Wang, Xiao;Terashi, Genki;Kihara, Daisuke
• 通讯作者: Kihara, Daisuke

Harnessing physicochemical properties of virus capsids for designing enzyme confined nanocompartments.

• DOI: 10.1016/j.coviro.2021.12.012
• 发表时间: 2022-03
• 期刊: Current opinion in virology
• 影响因子: 5.9
• 作者: Uchida M;Manzo E;Echeveria D;Jiménez S;Lovell L
• 通讯作者: Lovell L

Higher-Order VLP-Based Protein Macromolecular Framework Structures Assembled via Coiled-Coil Interactions

• DOI: 10.1021/acs.biomac.3c00410
• 发表时间: 2023-07-19
• 期刊: BIOMACROMOLECULES
• 影响因子: 6.2
• 作者: Hewagama，Nathasha D.;Uchida，Masaki;Douglas，Trevor
• 通讯作者: Douglas，Trevor

Cytochrome C with peroxidase-like activity encapsulated inside the small DPS protein nanocage

具有过氧化物酶样活性的细胞色素 C 封装在小型 DPS 蛋白纳米笼内

• DOI: 10.1039/d1tb00234a
• 发表时间: 2021
• 期刊: Journal of Materials Chemistry B
• 影响因子: 7
• 作者: Waghwani, Hitesh Kumar;Douglas, Trevor
• 通讯作者: Douglas, Trevor

Multilayered Ordered Protein Arrays Self-Assembled from a Mixed Population of Virus-like Particles

由病毒样颗粒混合群自组装的多层有序蛋白质阵列

• DOI: 10.1021/acsnano.1c11272
• 发表时间: 2022
• 期刊: ACS Nano
• 影响因子: 17.1
• 作者: Uchida, Masaki;Brunk, Nicholas E.;Hewagama, Nathasha D.;Lee, Byeongdu;Prevelige, Peter E.;Jadhao, Vikram;Douglas, Trevor
• 通讯作者: Douglas, Trevor