FET: Small: Simulation-guided design of heterochiral DNA nanostructures for biomaterials applications

FET：小型：用于生物材料应用的异手性 DNA 纳米结构的模拟引导设计

• 批准号: 2312215
• 负责人: Matthew Lakin
• 金额: $ 50万
• 依托单位: University of New Mexico
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-10-01 至 2026-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2312215&HistoricalAwards=false
• 关键词: FET; Small; Simulation; guided; design

DNA nanotechnology aims to use DNA as a scaffolding material to assemble engineered structures at the molecular scale, with nanometer precision. While most DNA nanotechnology molecules make use of DNA in the naturally occurring right-handed form known as D-DNA, an alternative uses chemically synthesized “left-handed” DNA, known as L-DNA, enabling the creation of DNA objects that twist in the opposite direction. A practical advantage of L-DNA molecules is that they resist degradation by enzymes in biological environments, which have evolved to recognize D-DNA specifically. On the other hand, while D-DNA molecules are more prone to degradation, they can interface directly with biological nucleic acids such as DNA and RNA. Therefore, it may be advantageous to combine the two forms of DNA into a single chiral hybrid, or “heterochiral”, form of DNA. This project will contribute to advancing the state of the art in DNA nanotechnology by studying the structure and function of such heterochiral nanostructures and by using this knowledge to engineer novel functional DNA nanodevices. Computational models and experimental results will be disseminated to the broader research community, and this project will train graduate and undergraduate students, including those from underrepresented groups, in interdisciplinary research skills. Public outreach efforts will be carried out in conjunction with local partner institutions.At the molecular level, a heterochiral DNA junction may have drastic effects on the stability and structure of a larger DNA nanotechnology object. This project will use molecular dynamics simulations to study the structures of heterochiral DNA double helices in the region of a chiral crossover, currently a poorly understood aspect of DNA structure given the novelty of these molecules. The results of these simulations will be used to make predictions about the behavior of heterochiral DNA, which will be validated experimentally. The project will produce engineering design rules for DNA nanostructures that combine D-DNA and L-DNA components, with the broad goal of controlling degradation pathways for these nanostructures in biological environments. These will be verified by studying the behavior of these components in model biological fluids that mimic conditions in vivo. The results obtained will enhance knowledge of DNA structure with regard to the interactions between different chiralities of DNA and will lead the way to practical applications of heterochiral DNA as a functional biomaterial for biomedical applications.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.

DNA纳米技术的目标是使用DNA作为支架材料，以纳米精度在分子尺度上组装工程结构。虽然大多数DNA纳米技术分子利用DNA的自然存在的右手形式称为D-DNA，替代使用化学合成的“左手”DNA，称为L-DNA，使DNA对象的创建扭转在相反的方向。L-DNA分子的一个实际优点是它们抵抗生物环境中酶的降解，这些酶已经进化到特异性识别D-DNA。另一方面，虽然D-DNA分子更容易降解，但它们可以直接与DNA和RNA等生物核酸接触。因此，将两种形式的DNA联合收割机组合成单一手性杂交或“异手性”形式的DNA可能是有利的。该项目将通过研究这种异手性纳米结构的结构和功能，并利用这些知识来设计新型功能性DNA纳米器件，从而推动DNA纳米技术的发展。计算模型和实验结果将传播给更广泛的研究界，该项目将培训研究生和本科生，包括来自代表性不足群体的学生，掌握跨学科研究技能。在分子水平上，异手性DNA连接可能会对较大DNA纳米技术物体的稳定性和结构产生重大影响。该项目将使用分子动力学模拟来研究手性交叉区域中的异手性DNA双螺旋的结构，鉴于这些分子的新奇，目前对DNA结构的了解甚少。这些模拟的结果将用于预测异手性DNA的行为，并将通过实验验证。该项目将为结合联合收割机D-DNA和L-DNA成分的DNA纳米结构制定工程设计规则，其广泛目标是控制这些纳米结构在生物环境中的降解途径。这些将通过研究这些成分在模拟体内条件的模型生物液体中的行为来验证。获得的结果将提高DNA结构的知识与DNA的不同手性之间的相互作用，并将导致异手性DNA作为生物医学应用的功能性生物材料的实际应用。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。