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Designing functional macromolecules

Abstract

Biology is driven by functional macromolecules, most notably proteins and non-coding RNAs. Learning how to design similarly functional macromolecules is a natural goal. Success will not only bring the ability to create new biological systems, but also the ability to more finely study and manipulate existing biological systems. In this thesis, I will describe two design projects that I pursued over the course of my PhD. The first is a project to remodel the backbone of a protein for the purpose of accurately positioning a catalytic sidechain. The second is a project to ligand-sensitive guide RNAs for the CRISPR-Cas9 system. There is of course much more to be done before we can say that we are able to design functional macromolecules, but the projects described herein move us closer to that goal.

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