Cooperativity Driven Communication through Noncovalent Networks in Biomimetic Systems

With the support of the Macromolecular, Supramolecular and Nanochemistry (MSN) Program in the Division of Chemistry, Professor Marcey Waters of the University of North Carolina (UNC) at Chapel Hill will develop new biomimetic model systems that imitate the complex behavior of proteins. This research aims to determine the molecular features that are necessary to create new stimulus-responsive molecules that mimic protein function, including molecular on-off switches for capturing/releasing other molecules, as well as self-assembly into nanospheres and nanofibers. This research seeks to provide better insight into protein function and provide guidelines for how to design new biomimetic "smart" materials. The broader impacts of this work will include interdisciplinary training for the students working on the project, as well as an outreach program to minority serving institutions that are part of the UNC system to build a network within North Carolina to promote pursuit of higher degrees in chemistry.Many proteins exhibit stimulus responsive behavior, as in allostery, conformational signaling, signal transduction, and complex protein assembly. These behaviors are accomplished via communication through a noncovalent network, but the molecular mechanisms of such communication are poorly understood. This research aims to provide fundamental insights into the design rules for biomimetic self-assembly and signal transduction, including their molecular and energetic requirements, as well as the role of both positive and negative cooperativity. Specifically, the Waters group will investigate the sequence-structure-assembly relationships in self-assembling coiled coil nanospheres and fibrils. An artificial signaling cascade will be developed for evaluation of the contribution of frustration in long-distance structural reorganization and responsive behavior of foldamers.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.