EAGER: Rapid DNA detection with a fluctuating surface-active peptide

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0923610TuIntellectual Merit:In this proposal, the PI addresses early stage exploration of the concept that peptide folding dynamics can be applied to accelerate the kinetics in selective binding processes. This is important because the ability to couple a particular illness with a specific biological marker, such as DNA, is increasing faster than the ability to rapidly detect those markers in a complex environment. A significant interdisciplinary effort has been invested in looking at the sequence specific detection of low molecular weight DNA markers, but these efforts still do not match the ability of native biological molecules to use dynamics to detect DNA markers in high molecular weight systems. This exploratory research idea focuses on how one can engineer a new biomimetic platform that applies accelerated kinetics to develop rapid sensing technologies. In order to accomplish this, one needs to balance the energy landscape of folded and unfolded peptide populations, which involves an inherently complex and risky set of experiments. The approach relies on an algorithm that combines binary sequence design and naturally occurring DNA binding sequences to develop novel peptides. These untested biomolecules are distinctly different from existing biomolecules, which are designed to stabilize a particular folded state. They will hybridize their previously developed tunable surface active peptide design with a DNA binding motif and measure the selectivity, avidity and kinetics of binding as a function of the fluctuating secondary structure. If these early stage experiments are successful, they will establish the molecular basis for designing peptides with fast kinetics and highly selective binding. This new paradigm for molecular design could then open doors to explore a variety of fundamental questions and technologies. The next step to transform this idea into a viable technology depends on (1) the ability to translate the fast kinetics into a sensitive and robust sensor and (2) the ability to translate the selectivity to a wide range of targets beyond DNA.Broader Impact:The scientific outcomes of the proposed work will contribute to the basic understanding of cooperative folding and binding processes that result in enhanced kinetics. Moreover, the proposed exploratory work is in its early stages, but successful experiments demonstrating the research idea will lead to a generation of biomolecules designed for dynamic behavior rather than static lock and key binding. These designs can be transformed into a general biotechnology based on quickly searching complex mixtures. Several elements of this program could be integrated into outreach efforts at CCNY. These efforts provide opportunities for students from the High School of Math, Science and Engineering (HSMSE) in Harlem to graduate students in CUNY to participate in research and learn about interdisciplinary science and engineering. The far reaching goals of this integrated research and teaching plan match CCNY's mission to provide quality education to a highly diverse student body (36% Hispanic, 30% black, 23% Asian and 11% white).