Solving Molecular Recognition Problems with Evolvable Peptide Motifs

Author: Austin, Ryan James

Year: 2007

Degree: Dissertation (Ph.D.)

Advisor: Roberts, Richard W.

Committee Members: Mayo, Stephen L.; Rees, Douglas C.; Dervan, Peter B.; Roberts, Richard W.

Option: Biochemistry and Molecular Biophysics

DOI: 10.7907/H8BY-M951

Abstract

Specific protein-nucleic acid and protein-protein recognition events are frequently mediated through the flexible binding surfaces of these polymers. The functional plasticity and sequence conservation of these surfaces suggests that they are highly evolvable molecular recognition sites. It may therefore be possible to develop discriminate ligands for many protein and nucleic acid targets by directed evolution of consensus ligand scaffolds or motifs. Here we review and present work on the development and use of peptide motifs to evolve high-specificity ligands toward flexible RNA-hairpin and G protein targets. The evolvabilities of these motifs and the compact arrangement of specificity-determining elements in selected sequences, demonstrate the economy of motif-based directed evolution approaches.

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