Understanding how and why long amino acid chains fold into complex, specific structures is one of the core questions of biochemistry. A complete answer would fuel a revolution in protein redesign, disease treatment and proteomics; the partial answer we already possess is paying dividends of this sort. Efficient investigations into folding mechanisms and fold-stabilizing interactions typically requires minimal model systems: amino acid chains that fold like proteins but are sufficiently small to be synthesized chemically and investigated by simpler spectroscopic techniques and more powerful molecular dynamics simulations. These small protein model systems are also good candidates for use as scaffolds for pharmacophore display, and some are capable of binding important biomolecules such as human amylin and ssDNA.

My work focuses primarily on the design of stable microprotein folds (largely β hairpins) by using appropriately placed tryptophan residues. Tryptophan is the rarest and the largest of the 20 standard amino acids, and it has proven exceptionally useful in fixing short chains of amino acids in well-defined structures. I have also probed the rationale for, and the limitations to, the fold stability conferred by tryptophan residues. These studies have provided a swath of useful model systems for probing the nature of protein folding, and an improved set of guidelines to follow in designing beta hairpin models and entire proteins.