2D Peptide and Protein Crystal Engineering for Functional Materials

功能材料的二维肽和蛋白质晶体工程

• 批准号: 2003962
• 负责人: Vincent Conticello
• 金额: $ 46.69万
• 依托单位: Emory University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2003962&HistoricalAwards=false
• 关键词: 2D; Peptide; Protein; Crystal; Engineering

Non-technical Summary: Two-dimensional (2D) nanomaterials (nanosheets) have potential advantages for the construction of devices of technological importance, such as chemical sensors, diagnostics, selectively permeable membranes, and catalytic and electronic scaffolds. However, the limited methods to control growth and rationally modify the resultant structures of these materials represents a significant impediment to progress in this field. Peptides and proteins are attractive candidates for the construction of these types of 2D materials since the control of sequence potentially permits the control of structure and function across length scales. One complicating factor is that proteins commonly display complex folding pathways, which can often result in limited control over the structure of the final material. An approach is proposed in which structural information from the Protein Data Bank (PDB), a vast library of freely available high-resolution protein structures, will be employed as the starting point to create novel classes of protein-based 2D materials. Layered protein structures will be identified in the PDB, in which close contacts are observed within the layer and long contacts are observed between layers. Computational and rational design methods will be used to strengthen interaction within a layer and further weaken or abrogate interactions between layers. Using this approach, one need not explicitly design the structure from first principles, but can instead create nanosheets from proteins that have a demonstrated propensity to form 2D layers. Several classes of materials targets will be investigated that would be useful from the perspective of potential applications in devices, including selectively permeable membranes and polar 2D crystals. These initial studies will validate the computational design approach and provide generally applicable methods to access novel classes of structurally defined 2D materials. Students involved in this project will gain valuable experience in cross-cutting research that enables a vertical consolidation of skill sets, including computational design, synthesis, and advanced methods of high-resolution structural characterization, that will be implemented for the design and fabrication of functional 2D nanomaterials. In addition, material related to the proposed research will be presented as content to illustrate concepts and learning objectives in a newly developed introductory undergraduate lecture course and laboratory experience on macromolecular chemistry at Emory University.Technical Summary: A heuristic approach is proposed to the design of structurally ordered 2D peptide nanomaterials that leverages the natural diversity of crystal structures in the Protein Data Bank (PDB). The PDB represents a rich trove of structural information on biomolecules. Many structures comprise layers of biomolecules, i.e., arrangements in which contact areas are more extensive within at least one crystallographically defined plane than between planes. In principle, the lateral interfaces within appropriately chosen crystal structures can be computationally optimized to enhance the cohesive interactions between protomers, while axial interactions are attentuated through weakening or blocking of the lamination of layers. This investigation comprises a proof-of-principle directed toward the hypothesis that crystallographically characterized layered structures can be used as a starting point to engineer and structurally diversify crystalline 2D peptide and protein assemblies through computational optimization of protomer interfaces. The research plan of this proposal encompasses three specific aims in support of the preceding hypothesis. The first two aims focus on the validation of this computationally-driven approach with respect to the design of two specific classes of 2D peptide materials targets that represent potential substrates for high value-added applications, namely open framework (porous) lattices and polar 2D crystals. We anticipate that success in these two aims will experimentally validate the feasibility and scope of this approach with respect to materials design, while simultaneously providing access to novel 2D nanomaterials. In the third specific aim, structural data resulting from the materials generated in specific aims 1 and 2 will be employed as input for additional rounds of computational design in order to create multi-component 2D nanostructures in which the tectons are chemically distinguishable and independently addressable on the nanoscale. In each specific aim, computational methods will be employed initially to optimize the structurally critical interfaces between protomers. Candidate peptides will be synthesized and screened using higher throughput, low-resolution experimental methods. Suitable structures will be subjected to high-resolution structural analysis, primarily using cryo-EM 2D reconstruction with direct electron detection and, when applicable, single-crystal diffraction analysis.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.

非技术总结：二维（2D）纳米材料（纳米片）具有潜在的优势，用于构建具有技术重要性的设备，如化学传感器，诊断，选择性渗透膜，催化和电子支架。然而，控制这些材料的生长和合理地改变所得结构的有限方法代表了该领域进展的重大障碍。肽和蛋白质是用于构建这些类型的2D材料的有吸引力的候选物，因为序列的控制潜在地允许跨长度尺度控制结构和功能。一个复杂的因素是蛋白质通常显示复杂的折叠途径，这通常会导致对最终材料结构的控制有限。提出了一种方法，其中结构信息从蛋白质数据库（PDB），一个巨大的图书馆免费提供的高分辨率蛋白质结构，将被用作起点，以创建新的类蛋白质为基础的二维材料。将在PDB中识别分层蛋白质结构，其中在层内观察到紧密接触，并且在层之间观察到长接触。计算和合理的设计方法将用于加强层内的相互作用，并进一步削弱或消除层间的相互作用。使用这种方法，人们不需要从第一原理明确设计结构，而是可以从具有形成2D层的倾向的蛋白质中创建纳米片。几类材料的目标将被调查，这将是有用的，从设备的潜在应用的角度来看，包括选择性渗透膜和极性2D晶体。这些初步研究将验证计算设计方法，并提供普遍适用的方法，以访问结构定义的2D材料的新类别。参与该项目的学生将获得跨领域研究的宝贵经验，这些研究能够垂直整合技能组合，包括计算设计，合成和高分辨率结构表征的先进方法，这些方法将用于设计和制造功能性2D纳米材料。此外，与拟议研究相关的材料将作为内容呈现，以说明埃默里大学新开发的介绍性本科讲座课程和实验室大分子化学经验中的概念和学习目标。技术摘要：提出了一种启发式方法来设计结构有序的2D肽纳米材料，该方法利用了蛋白质数据库（PDB）中晶体结构的自然多样性。PDB代表了生物分子结构信息的丰富宝库。许多结构包括生物分子层，即，其中接触区域在至少一个晶体学限定的平面内比在平面之间更广泛。原则上，适当选择的晶体结构内的横向界面可以通过计算优化以增强原聚体之间的内聚相互作用，而轴向相互作用通过层的层压的弱化或阻挡而减弱。这项调查包括一个原则的证明指向的假设，即结晶表征的层状结构可以作为一个起点，工程师和结构多样化的结晶2D肽和蛋白质组装体通过计算优化的原聚体接口。本提案的研究计划包括支持上述假设的三个具体目标。前两个目标集中在验证这种计算驱动的方法相对于两个特定类别的2D肽材料的目标，代表潜在的高附加值的应用，即开放的框架（多孔）晶格和极性2D晶体基板的设计。我们预计，这两个目标的成功将通过实验验证这种方法在材料设计方面的可行性和范围，同时提供新型2D纳米材料。在第三个具体目标中，具体目标1和2中生成的材料产生的结构数据将用作额外几轮计算设计的输入，以创建多组分2D纳米结构，其中结构元在化学上是可区分的并且在纳米尺度上可独立寻址。在每一个具体的目标，计算方法将最初优化结构关键的接口之间的原聚体。将使用更高通量、低分辨率的实验方法合成和筛选候选肽。合适的结构将进行高分辨率的结构分析，主要使用冷冻EM 2D重建与直接电子检测，并在适用的情况下，单晶衍射分析。该奖项反映了NSF的法定使命，并已被认为是值得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的支持。

项目成果

Peptide-based nanomaterials: Building back better & beyond

• DOI: 10.1016/j.cossms.2023.101066
• 发表时间: 2023-04
• 期刊: Current Opinion in Solid State and Materials Science
• 影响因子: 11
• 作者: V. Conticello

Shape-Shifting Peptide Nanomaterials: Surface Asymmetry Enables pH-Dependent Formation and Interconversion of Collagen Tubes and Sheets

• DOI: 10.1021/jacs.0c08174
• 发表时间: 2020-11-25
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Merg, Andrea D.;Touponse, Gavin;Conticello, Vincent P.
• 通讯作者: Conticello, Vincent P.