Past Results

2017

Davey et al. (2017) Nature Chemical Biology 13, 1280-1285.

This manuscript presents the first demonstration of the rational design of proteins that can spontaneously exchange between two predefined conformational states in the absence of an external stimulus, and on a timescale relevant to function. To achieve this result, we developed a broadly-applicable computational method to engineer protein dynamics that we term meta-multistate design (meta-MSD). We used meta-MSD to design spontaneous exchange between two novel conformations introduced into the global fold of protein G domain β1 (Gβ1). The designed proteins, named DANCERs, for Dynamic And Native Conformational ExchangeRs, are stably folded and exchange between predicted conformational states on the millisecond timescale. Our new method for design of conformational exchange paves the way to the design of proteins with a more versatile range of functions than was previously possible, such as those that must adopt more than one conformational state (e.g., enzymes, molecular rotors, biosensors).

2016

Pandelieva AT et al. (2016) ACS Chemical Biology 11, 508-517.

2016/09/01. We recently used rational design to increase the quantum yield and brightness of red fluorescent proteins (RFPs) by rigidifying their chromophore via the creation of a triple-decker motif of aromatic rings (see figure below). The best mutant identified displayed an over three-fold improvement relative to the parent RFP and was isolated following the screening of only 48 mutants, a library size that is several orders of magnitude smaller than those previously used to achieve equivalent gains in quantum yield in other RFPs.