Dr. Keating’s research at MIT involves working to understand how protein sequences and structures encode interaction specificity. Her lab uses computational and experimental methods to measure protein interactions in high throughput, predict new interactions, and design proteins and peptides with novel interaction properties. Early research in the Keating lab involved a deep dive into the interactions of b-ZIP transcription factors, including a study of how interactions among these proteins have evolved over a billion years. The Keating lab’s “SYNZIP” proteins comprise a set of native and designed coiled coils that form rod-like heterodimers that can be used for a variety of molecular engineering applications, including to make programmed nanoscale structures. A particular interest of the group lies in designing high-affinity yet selective binders/inhibitors that can target just one or a few paralogs out of a larger family of related proteins. The lab has had considerable success combining computational and experimental methods to design helical peptides for binding to bZIP proteins and to Bcl-2 family proteins that control programmed cell death. More recently, the lab started to study modular protein domains that bind to short linear motifs, working to understand how such interactions are used in biology for signaling and scaffolding, and how they can be perturbed using rational protein design.