New Strategy For Designing Light Sensitive Proteins

The study developing a new strategy for designing light sensitive proteins; Such proteins, also known as optogenetic tools, can be switching on and off through light impulses; thus triggering specific cellular processes. They can, for example, be used to analyse and control how signals are transmitted by nerve cells. By this developing an optogenetic tools have been pretty much forced to resort to trial-and-error.

A combination of computer aided and experimental methods has now paved the way for a more targeted approach. An example of an optogenetic tool is the protein melanopsin. It can be switched on and off by two light signals in different colours. Often, more than just one optogenetic tool is requiring; for example if two different processes have to be controlling in a cell independently of each other.

A hybrid strategy for targeted protein engineering of melanopsin and other optogenetic tools. To this end, the researchers combined computer-aided calculating methods with electrophysiological measurements. Using quantum chemistry computer simulations, they calculated the specific light colour required to activate a protein. Thus, they determined how individual protein building blocks resp.

Light sensitive proteins

But the exchange of individual protein building blocks affects the light colour. The computer simulation generated a list of protein variants that qualify as potential optogenetic tools. Subsequently, the researchers used electrophysiological measurements to analyse the promising candidates with regard to their optogenetic potential.

This including light sensitivity, i.e. how much light is needing to switch the protein on and off; as well as the speed and selectivity at which mechanisms are implementing or terminating after the activation of the switch. A good optogenetic tool can be switching on and off in quick succession at low light intensity. Using the well researching optogenetic tool Channelrhodopsin-2; the team validated the new hybrid strategy.

Selective molecular light switch

For this protein, the researchers used computer simulation to verify how an exchange of protein building blocks would affect the activating light colour. The prognoses corresponded with the values measured in experiments. Melanopsin is a promising optogenetic tool that functions as a selective molecular light switch for G protein‐coupled receptor pathways.

But the group exchanging specific protein building blocks in melanopsin, thus manipulating the light colour for molecule activation, without impairing the protein function. The light colour that activates the usual melanopsin version overlaps with that of many other optogenetic tools which is why they cannot be used in combination.