Research

Design of Protein Sensors & Actuators

A generalizable, simple design of biosensors for different chemical and physical signals comprises a "sensor" and an "effector" domains. Sensor domains are naturally occurring or engineered proteins (or domains) which undergo conformational changes upon a trigger signal. Here, effector domains are reversible, conformation-specific protein binders obtained by protein display and high-throughput screening or computational design. Our demonstrated examples include chemically (ligand) induced dimerization (CID) and light induced dimerization (LID) systems.

To screen conformation-specific mini-binders, we built vastly diverse synthetic combinatorial libraries (> 109) based on immunoglobulin, non-immunoglobulin, and computationally designed (by the David Baker lab) scaffolds (MD simulation movies were made by Dr. Weiwei Xue).