New ways to identify proteins support drug development

All living cells contain proteins with different functions depending on the type of cell. Researchers at the University of Gothenburg have found a way to identify proteins without even looking at their structure. Their method is faster, easier, and more reliable than the previous method.

Today, the prevailing view is that it is the structure of each protein that controls its function in the cell. Atomic order, which means how the atoms are arranged in a protein, creates the structure and shape of the protein. But there are many proteins that do not have a well-defined structure.

Researcher Gergely Katona has developed a new method in which proteins are scanned based on the number of amino acids (or the number of different atoms) they contain to identify them and their function instead of identifying them based on their structure. With this scanning method, researchers can predict with relative reliability which combination of amino acids is required to bind to the survivin protein. The result is about 80 percent reliability, which is better than when you use the primary structure of a protein for identification. The results are now published in the scientific journal iScience.

Structure is less important

Several thousand peptides containing 15 amino acids have been tested and researchers can conclude that it is the amino acid content that influences their binding to survivin, whereas the peptide structure is of almost no significance.

“Computing simple things is often a successful method in science. Here we count the number of amino acids and are able to predict protein function very well,” said Gergely Katona.

The researchers saw an advantage with this protein scanning method. Machine learning (AI) is also accelerating the process of linking the number and type of amino acids to specific functions. This in turn means that the development of new biologic drugs can be accelerated.

In the researchers’ experiments with this new scanning method, an entirely new function of the survivin protein was also discovered. This protein is especially prominent in embryonic cells and prevents programmed cell death. But in cancerous tumors, survivin becomes disordered and thus facilitates cancer development.

Useful in cancer research

Researchers have now seen that survivin directly affects another protein, PRC2, which switches various functions in the DNA on and off within the cell, like a kind of programming. Dysfunctional PRC2 may also be associated with various forms of cancer. Current cancer drugs target survivin and PRC2, but with the recently discovered link between survivin and PRC2, they may need to be designed differently to avoid serious side effects.

“We saw that if we suppressed the survival rate, activity in PRC2 increased. The dream of a pharmaceutical company is to find the right target in a series of atoms to be able to balance the two proteins,” said Gergely Katona.