BPS2026 – Proteins with new-to-nature backbones

As far as we know, the translational apparatus has evolved for billions of years to perform a single chemical reaction-formation of an amide bond between two α-amino acids brought into proximity by tRNAs within the ribosome active site. This reaction produces sequence-defined polymers of α-amino acids, the molecules we call proteins. One can imagine three different strategies to expand the chemistry of translation to generate materials that are not strictly polymers of α-amino acids. These new-to-nature products offer opportunities for expanded function, predictable structure, tunable stability, and orthogonal reactivity. This lecture will describe recent progress and the critical role of biophysics in advancing each of these three strategies.