I am using the resources of the Computer Graphics Laboratory to guide mutagenesis and phage library design onto a platform de novo designed four helix bundle protein. The modest resolution crystal structure for this de novo designed four-helix bundle proto-type has been published. Another crystal form was found which yielded a data set of higher resolution which I am solving. I am using this unique structure to understand some of the protein design principles that were originally introduced. Further studies include using this new structural result to design mutations using MidasPlus and gene manipulation software. The direction of the mutation currently focuses on understanding cooperativity in protein unfolding and what leads to fold specificity. Strictly structural studies include testing whether this simple protein can be a scaffold for studying protein-protein interactions secondary structure interfaces of difficult to study proteins, such as extracellular portion of signalling membrane proteins with well-defined functional domains. Biochemical and structural studies will follow the new proteins. The phage display experimental design will focus on adding function to understand the nature of the basic principles which allow proteins to carry minimal function.
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