Over 75 percent of proteins present at the surface of human cells are covered by glycans. These sugar-like molecules form very dynamic protective shields around the proteins. However, the mobility and variability of the sugars make it difficult to determine how these shields behave or how they influence the binding of drug molecules.
Now, researchers at the Max Planck Institute have developed an algorithm to solve this challenge. The algorithm, GlycoSHIELD, enables fast but realistic modeling of the sugar chains present on protein surfaces.
Until now forecasting the structure of sugar layers using computer simulations was only possible with expert knowledge of special supercomputers. In many cases, thousands or even millions of computing hours were required. Meanwhile, GlycoSHIELD provides a fast, environmentally friendly open-source alternative.
“Our approach reduces resources, computing time, and the technical expertise needed," says project leader Mateusz Sikora. “Anyone can now calculate the arrangement and dynamics of sugar molecules on proteins on their personal computer within minutes, without the need for expert knowledge and high-performance computers.”
The software can not only be used in research but could also be helpful for the development of drugs or vaccines, for example, in immunotherapy for cancer.
The authors created and analyzed a library of thousands of most likely 3D poses of the most common forms of sugar chains on proteins found in humans and microorganisms. Using long simulations and experiments, they found that for a reliable prediction of glycan shields, it is sufficient that the attached sugars do not collide with membranes or parts of the protein. The algorithm is based on this discovery.