Comparative study between de novo proteins and randomly produced proteins

May 23, 2023 | Biotechnology

A team of Czech and German scientists, from the University of Prague and University Münster, have conducted experiments involving comparisons between de novo proteins and computer-generated proteins regarding their stability and solubility. They were able to find small differences deviating from predictions.

In a series of experiments, they compared the two proteins: 1,800 candidates for de novo proteins from fruit flies and humans, located in non-genetic parts of the genome, and randomly sequenced proteins. With the aid of numerous computer programs, predictions relating to structure made very similar classifications of both classes and it enabled them to predict the protein’s properties. For the experimental analysis, they were able to produce the proteins and examined them by means of mass spectrometry.

In another round of experiments, they added a protein-degrading enzyme and this allowed them to test the number of proteins that were actually degraded after which they drew conclusions about their stability. In investigating the protein’s solubility, they used a molecular transport mechanism, with Escherichia coli an indicator. The soluble proteins were then determined closely through next generation DNA sequencing.

Results in the lab experiments showed that the de novo proteins displayed a slightly higher solubility on average based on secondary structure. They can be better integrated into the cell as compared to what was expected from random computer-generated proteins, suggestive of natural selection occurring in the earlier phases of this protein’s emergence.

Aside from solubility, the ability of the proteins is also being examined by the researchers. This ability plays a critical role in a variety of diseases and recent studies have already shown the association of de novo proteins with these diseases. Further research on these proteins will allow us to understand more on this protein’s role in the development of disease.