Large enhancement of response times of a protein conformational switch by computational design
Lillian Chong and her colleagues have recently reported, in the Journal of Nature Communications, a computational design strategy in synergistic combination with biophysical experiments to rationally improve the response time of an engineered protein-based Ca2+-sensor in which the switching process occurs via mutually exclusive folding of two alternate frames. This strategy identifies mutations that increase switching rates by as much as 32-fold, achieving response times on the order of fast physiological Ca2+ fluctuations. This computational design strategy is general and may aid in optimizing the kinetics of other protein conformational switches.