Proteins are the molecules that underlie the broad range of exquisite functions in biology. Proteins and their assemblies define the physical and mechanical properties of cells and tissues, regulate all signaling processes, perform all biosynthetic functions, and are responsible for transducing chemical and electromagnetic energy, among many other roles. The functions of proteins are defined exclusively by the sequences and three-dimensional structures of their polypeptide chains. These structures provide active sites capable of catalyzing specific chemical reactions and have surfaces that are complementary to those of other molecules and allow protein-ligand interactions. It is now clear that many protein functions are regulated by conformational changes in the protein, including those that are regulated by specific stimuli and those that represent thermal fluctuations in the protein structure. Yet, for the approaches now used to develop proteins having novel functions, very few are based on engineering proteins with regulated conformational changes. This gap has its roots in the significant challenges in identifying molecular strategies that can effect defined changes in the motions of protein domains, and in developing syntheses of proteins having the relevant stimuli-responsive dynamic bonding chemistries. These deficiencies in turn define two grand challenges: (1) How does one design reversible covalent chemistries that can be used to regulate the conformations of protein-based structures and (2) How can experimental and computational approaches be combined to design and demonstrate large-scale conformational changes in protein-based structures.
|Effective start/end date||7/30/18 → 7/29/23|
- Army Research Office (W911NF1810200/P00005)
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