Cooperativity Driven Communication through Noncovalent Networks in Biomimetic Systems

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With the support of the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Professor Marcey Waters of the University of North Carolina at Chapel Hill will develop biomimetic model systems that mimic the complex behavior that regulates protein function. Many proteins function as molecular machines that respond to stimuli with molecular on-off switches. This research seeks to uncover the molecular features that are necessary to create new stimulus-responsive molecules that mimic the behavior seen in proteins. The findings from this work have the potential to provide better insight into biomedically relevant protein behavior, but to also provide guidelines for how to create new biomimetic "smart" materials. The broader impacts of this work include broad interdisciplinary training for the students working on the project, as well as the development of new program that connects chemistry majors doing independent research with younger students to provide peer role models and guidance on how to pursue research, with the goal of increasing the number of students from underrepresented groups that engage in research in the chemistry and chemical biology.Proteins are complex molecules that display a wide range of behaviors beyond binding and catalysis, including stimulus response involving long-distance structural rearrangement as in allostery, conformational signaling, and signal transduction. These behaviors are accomplished via communication through a noncovalent network, but the molecular mechanisms of such communication are poorly understood. This research aims to develop predictive model systems with a responsive noncovalent network to establish the molecular requirements for achieving communication through a noncovalent network, including the role of both positive and negative cooperativity. These model systems have the potential to bridge the gap between minimalist models and complex proteins to gain molecular level insight into these responsive systems.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.