0738 GMT June 16, 2019
According to interestingengineering.com, the created protein was able to ‘bind and activate a compound similar to that housed inside the green fluorescent protein.’ This is a huge step forward for science, where previous attempts at making small-molecule binding proteins had been limited by the practice of proteins already existing in nature.
This recent breakthrough opens the doors to scientists being able to create proteins unlike any other found in nature. Custom-designed proteins can be made with a high precision and the ability to bind to and act on specific small molecule targets.
This from scratch or ‘de novo’, technique has potential applications in research, medicine and industry.
Senior author David Baker explained, "The successful de novo design of custom-built proteins with small-molecule binding activity sets the stage for the creation of increasingly sophisticated binding proteins that will not have the limitations seen with proteins that have been designed by altering existing protein structures."
Before the scientists could even start to make the protein from scratch they first had to create from scratch a cylinder-shaped protein called a beta-barrel. The shape is perfect for the task as one end of the cylinder works to stabilize the protein, while the other works as a binding site for the target molecule.
The scientist used a software platform, developed in the Baker lab, called Rosetta to design the new protein. The program can predict what shape a chain of amino acids will assume after synthesis and can assist in predicting how altering individual amino acids along the chain may alter the final shape.
This predictive power makes it possible to test out different combinations of amino acids to design a protein with the desired shape and function. In addition to this predictive software, the scientist made use of a powerful new docking algorithm, called ‘Rotamer Interaction Field’ (RIF), which was developed by William Sheffler, a senior research scientist in the Baker lab.
The algorithm ‘identifies all potential structures of cavities that fulfill the prerequisites for binding specific molecules.’ By utilizing the algorithm and the software program, the scientist successfully developed their custom-designed protein that could avidly bound and activate the DFHBI compound.