Designing the future by making proteins “dance”

Posted on Tuesday, July 31, 2018

Microscope to see the DANCER proteins

Discovery paves way to broad range of applications in pharmaceuticals, agri-food and biotech.

A team of researchers led by University of Ottawa Professor Roberto Chica of the Department of Chemistry and Biomolecular Sciences has developed a way to solve a long-held biotechnology limitation by creating “flexible” engineered proteins — or designer proteins — that can modify their structure to meet a desired function.

Proteins are used in a wide range of applications in industry, medicine and research. Enzymes, a type of protein, play an essential role in the production of drugs for the treatment of diabetes, for example. Proteins are also involved in the manufacture of portable disease diagnostic devices and even lactose-free milk.

However, proteins found in nature often have features that limit their efficiency in certain desired applications, such as the enzymes in clothing detergents, which need to be tailored to operate in specific temperature ranges, pH levels and in combination with other chemicals.

This is where protein engineering comes into play.

“Proteins found in nature are dynamic molecules that often undergo structural changes in order to carry out the complex molecular processes required for life,” explains Professor Chica. “Just like machines, proteins need to move to accomplish their tasks. However, this has been difficult to reproduce with engineered proteins. The standard laboratory techniques to engineer proteins could only produce static or ‘rigid’ proteins that are exponentially less efficient than ‘flexible’ natural proteins.”

DANCER protein created by uOttawa professor Roberto Chica

Devising a computational method called meta-multistate design, Professor Chica and his team created “flexible” proteins, aptly named DANCERs (which stands for dynamic and native conformational exchangers), that spontaneously change between two target structures, paving the way for more complex protein functions than previously possible.

“Our discovery opens the door to the development of sustainable, efficient and affordable designer proteins to help address or solve a multitude of issues,” adds Chica.

Whether for the production of biofuels, antibodies or pest-resistant crops, Canada’s bio-economy sector, estimated at $80 billion annually and which supports more than 1 million jobs, relies heavily on a number of technologies that require laboratory engineered proteins. The ability to design protein machines with enhanced functionalities will help the Canadian bio-economy meet the increasing demands it faces that result from climate change and an ever-increasing world population.

Read the research article, Rational design of proteins that exchange on functional timescales, published in Nature Chemical Biology (2017, volume 13, pp. 1280–1285)


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