Can proteins perform logic?

The main role of many proteins is to transmit and process information in living cells. These processes involve other molecules called regulatory ligands that bind to specific sites on the surface of the protein. It has been known for almost 50 years that a typical protein can switch between an inactive and an active state as the concentration of the ligand varies. These states could be used to represent the “0”s and “1”s of binary logic, but proteins are not true logic gates because a large change in concentration is needed to switch them from one state to another.

Now, Ian Graham and Thomas Duke of Cambridge University have shown how, in theory, certain proteins can bind two different ligands at the same time to perform all the elementary logic functions, including AND, OR, XOR and NOT XOR. These proteins can act as individual logical elements because their output depends on two inputs – the concentrations of the ligands. Moreover, when the proteins cluster together, the response is further enhanced. The clusters can thus act as logic gates whose activity can be abruptly switched from fully active to fully inactive as the concentrations of the ligands pass certain thresholds.

Graham and Duke cite the bacteria E. Coli as an example – different types of receptor proteins bind various ligands, such as glucose and lactose, to produce a well-defined response. The switching can be observed by watching the bacteria “light up” as the concentration of ligands increase because they contain genetically modified fluorescent proteins.

“The interesting bit is the switch-like property of the receptor cluster,” says Graham. “Before, all experiments were done on cell populations, so the error bars in the experiments obscured this exciting fact: that the receptor proteins act as an ultra-sensitive three-state switch that is ‘null’ in the absence of a stimulus, ‘on’ if the ligand concentration increases and ‘off’ if it decreases.”