EFRI-BSBA: Engineering Synthetic Mimics of DNA-Protein Recognition Systems

EFRI-BSBA：DNA-蛋白质识别系统的工程合成模拟

• 批准号: 0938019
• 负责人: Ronald Larson
• 金额: $ 199.99万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0938019&HistoricalAwards=false
• 关键词: EFRI; BSBA; Engineering; Synthetic; Mimics

ABSTRACT: EFRI-BSBA: Engineering Synthetic Mimics of DNA- Protein Recognition SystemsProposal # 0938019PI: Larson, Ronald G.The research objective of this collaborative project is to create artificial "DNA" consisting of charged lines or nanowires deposited on a silicon substrate, with charged synthetic nanoparticles functioning as synthetic "proteins." Proteins transcribe DNA into RNA, regulate genes, and replicate DNA, all with remarkable efficiency and precision. To do so, in each cell, thousands of proteins scan continuously millions of bases of DNA, and bind firmly only when encountering precise sequences of six to twenty base pairs. This superb sequence discrimination is achieved through a combination of simple physical forces - primarily electrostatic, hydrophobic, hydrogen bonding, and van der Waals. These forces result in the diffusion of positively charged proteins along negatively charged DNA, binding firmly only when a precise pattern of charged, polar, and hydrophobic regions on the protein complements sites on DNA having the appropriate base sequence. If this mechanism could be harnessed within synthetic systems, it would represent a transformative breakthrough that would open the door to wide-ranging applications in the areas of nanoscale sensing, actuation and programmed assembly. Examined in this project will be both charged organic PAMAM dendrimers and surfactant-coated inorganic CdSe and CdTe nanoparticles, and engineer their charge distributions, as well as hydrogen bonding and van der Waals interactions to produce weak binding to generic DNA sequences or line charge distributions and strong binding to specific ones, using molecular dynamics simulations to guide the design. The research will aim to engineer both the one-dimensional search and the binding at specific sites by patterned nanoparticles to complementarily patterned lines on silicon. This research also intends to drive reactions upon firm binding, including photoemission, thus taking the first steps towards precise nano-actuation. Broader impacts include responding to a "grand challenge" by laying a foundation for the diagnosis, repair, and ultimately self-fabrication of nanomaterials and nanocircuitry. The PIs will also develop an outreach and minority recruiting program using a miniaturized "Biological Mimics Roadshow" for use in the classroom in collaboration with U-of-M's IDEA Institute. This program will be supplemented by running residential summer science camps for Detroit minority high school students, which will introduce high school minority students to some of the most exciting science and engineering, and encourage their pursuit of these fields.

摘要：EFRI-BSBA：工程合成模拟DNA-蛋白质识别系统提案#0938019 PI：拉森，罗纳德G.该合作项目的研究目标是创造人工“DNA”，由沉积在硅衬底上的带电线或纳米线组成，带电的合成纳米颗粒作为合成“蛋白质”。“蛋白质将DNA转录成RNA，调节基因并复制DNA，所有这些都具有显着的效率和精度。为了做到这一点，在每个细胞中，成千上万的蛋白质连续扫描数百万个DNA碱基，只有在遇到6到20个碱基对的精确序列时才能牢固地结合。这种极好的序列区分是通过简单的物理力的组合实现的--主要是静电力、疏水力、氢键和货车范德华力。这些力导致带正电荷的蛋白质沿着带负电荷的DNA扩散，仅当蛋白质上的带电荷、极性和疏水区域的精确模式与具有适当碱基序列的DNA上的位点互补时才牢固结合。如果这种机制可以在合成系统中利用，它将代表一个变革性的突破，将为纳米级传感，驱动和编程组装领域的广泛应用打开大门。在这个项目中检查将是带电的有机PAMAM树枝状聚合物和表面活性剂涂覆的无机CdSe和CdTe纳米粒子，并工程师的电荷分布，以及氢键和货车范德华相互作用，以产生弱结合到通用DNA序列或线电荷分布和强结合到特定的，使用分子动力学模拟来指导设计。该研究的目标是设计一维搜索以及图案化纳米颗粒与硅上互补图案线在特定位点的结合。这项研究还打算在牢固结合时驱动反应，包括光电发射，从而朝着精确的纳米驱动迈出第一步。更广泛的影响包括通过为纳米材料和纳米电路的诊断、修复和最终的自我制造奠定基础来应对“重大挑战”。PI还将与密歇根大学的IDEA研究所合作，利用微型化的“生物模拟路演”开发一个外展和少数族裔招募计划，供课堂使用。该计划将通过为底特律少数民族高中学生举办住宅夏季科学夏令营来补充，这将向少数民族高中学生介绍一些最令人兴奋的科学和工程，并鼓励他们追求这些领域。