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

摘要：EFRI-BSBA：DNA-蛋白质识别系统的工程合成模拟物Proposal#0938019PI：Larson，Ronald G.这一合作项目的研究目标是创建由沉积在硅衬底上的带电线路或纳米线组成的人造DNA，并将带电合成纳米颗粒用作合成“蛋白质”。蛋白质将DNA转录成RNA，调节基因，复制DNA，所有这些都非常高效和精确。为了做到这一点，在每个细胞中，数千种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会牢固地结合。这种卓越的序列识别是通过简单的物理作用力的组合实现的，主要是静电、疏水、氢键和范德瓦尔斯。这些作用力导致带正电的蛋白质沿着带负电的DNA扩散，只有当蛋白质上的带电、极性和疏水区的精确模式与DNA上具有适当碱基序列的位置互补时，才能牢固地结合。如果这种机制能够被利用到合成系统中，它将是一项革命性的突破，将为纳米级传感、驱动和程序化组装领域的广泛应用打开大门。该项目将研究带电的有机PAMAM树枝状大分子和表面活性剂包裹的无机CdSe和CdTe纳米粒子，并利用分子动力学模拟来指导设计，并设计它们的电荷分布以及氢键和范德华相互作用，以产生与通用DNA序列或线电荷分布的弱结合和与特定DNA序列的强结合。这项研究的目标是设计一维搜索，并通过图案化纳米颗粒与硅上互补的图案化线条在特定位置结合。这项研究还打算在牢固的结合上推动反应，包括光电子发射，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、修复和最终自制造奠定基础来应对“重大挑战”。PIS还将与密歇根大学的IDEA研究所合作，开发一项外展和少数族裔招募计划，使用微型“生物模拟路演”在课堂上使用。该计划将通过为底特律少数民族高中生举办住宿夏季科学夏令营来补充，该夏令营将向高中生介绍一些最令人兴奋的科学和工程知识，并鼓励他们追求这些领域。

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.