Semibiological molecular machine with an implemented "AND" logic gate for regulation of protein folding

A semibiological molecular machine with an implemented "AND" logic gate was developed, which was capable of controlling the folding process of proteins in response to ATP and light as input stimuli. The molecular design made use of a genetically engineered chaperonin GroEL bearing, at both entrance parts of its cylindrical cavity, cysteine residues, which were functionalized by an azobenzene derivative to construct photoresponsive mechanical gates (azo-GroEL). This engineered chaperonin trapped denatured green fluorescent protein (GFP_denat) and prohibited its refolding. However, when hosting azo-GroEL detected ATP (input stimulus 1) and UV light (input stimulus 2) at the same time, it quickly released GFP_denat to allow its refolding. In contrast, reception of either input stimulus 1 or 2 resulted in only very slow or no substantial refolding of GFP_denat. Implementation of such "AND" logic gate mechanisms in mechanically driven biomolecular systems is an important step toward the design of secured drug delivery systems.