Proteins with non-trivial topology - knotted proteins - provide the greatest challenge in protein folding. Therefore, understanding the mechanisms of knot formation and stability will have a major impact on our understanding of protein folding and functional dynamics at large. This project is focused on understanding and characterizing the underlying physical principles responsible for knot formation in the alpha/beta knot methyltransferase family of proteins. Research will focus on a monomeric member of the family, firmly simplifying folding analyses. This discovery of a monomeric knotted protein will allow the dissection of the underlying principles that lead to knot formation and the impact on protein function. Consequently, these studies will provide the fundamental basis for future protein design efforts.
BROADER IMPACT. This project bridges the fields of mathematics, biology, chemistry, and physics, inspiring cutting-edge interdisciplinary collaborations, and will be important in defining the key problems in folding for the next decade. Graduate students will be exposed to chemistry, mathematics, physics and biology through this study and will be provided with valuable experimental and theoretical skills (molecular biology, protein biochemistry, chemical synthesis, coordination chemistry, spectroscopic techniques, electrochemistry, crystallography) that will better assist them as they tackle complex scientific problems later in their careers.
This project is being supported jointly by the Physics of Living Systems Program in the Physics Division and by the Molecular Biophysics Program in Division of Molecular and Cellular Biosciences.
