Beyond Molecular Beacons: Optical Sensors Based on the Binding-Induced Folding of Proteins and Polypeptides

A beacon in the night! The binding‐induced folding of otherwise unfolded biopolymers may prove a generic signal‐transduction mechanism for protein‐ and polypeptide‐based biosensors. An example of such a biosensor is illustrated here. Many polypeptides and small proteins can be readily engineered such that they only fold upon binding a specific target ligand. This approach couples target recognition with a considerable change in polymer structure and dynamics. Recent years have seen the development of a number of biosensors that couple these large changes to readily measurable optical (fluorescent) outputs. These sensors afford the detection of a wide variety of macromolecular targets including proteins, polypeptides, and nucleic acids. Here we describe the design of such biosensors, from the first iterations as protein engineering experiments, to the development of biosensors targeting a range of protein and nucleic acid targets. A beacon in the night! The binding‐induced folding of otherwise unfolded biopolymers may prove a generic signal‐transduction mechanism for protein‐ and polypeptide‐based biosensors. An example of such a biosensor is illustrated here.