The improvement of stability of engineered proteins is an important area of research given the several applications of proteins that require them to be very stable. It is known that there is a generally inverse relationship between protein stability and flexibility. Proteins move around in solution and have intrinsic flexibility, which, in turn, is critical for their functionality. In this way, the relationship between stability, function, and dynamics is very complex, and the underlying principles governing this relationship are yet to be fully elucidated. Engineered, highly stable, homeodomain DNA-binding proteins have been designed to retain their functionality and, in some cases, have higher affinity to their cognate DNA partners than their natural counterparts. This project compares the stability and function of a consensus homeodomain, natural homeodomains, and rationally-designed mutants to lay the foundation for studying the complex relationship among these properties of proteins.
