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

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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.