Many Studies Show that A Computational Method that Thermally Stabilizes G-protein-coupled Receptors is Promising in The Analysis of Receptor Structures

Researchers from the Moscow Institute of Physical Science and Technology (MIPT), the Skolkovo Institute of Science and Technology (Skoltech) and the University of Southern California (USC) have developed a new computational method to design thermally stable G Protein-coupled receptors (GPCRs), which are very effective in developing new drugs. This method has been shown to be useful for obtaining the structure of several major human receptors. An overview of this new approach was published in the Current Opinion on Structural Biology.



Receptors are molecules that capture and transmit signals and play a key role in human regulation. Receptor GPCRs are one of the most well-known families of human proteins involved in vision, olfactory, immune response and brain processes, making them important drug targets. As a class of receptors, these researchers need to understand their structure in great detail. It is a more challenging task to study receptors which become unstable when detached from the cell membrane. It is largely due to the computational methods that help to accurately predict the vulnerable sites of the receptor and make it more stable changes.


Professor Petr Popov, the first author of this study from the G-protein coupled receptor structural biology laboratory of the Moscow Institute of Physical Science and Technology, explained, “The structural study of GPCRs has high scientific and application value because these proteins are targets of 30% to 40% of drugs. Our approach relies on several GPCR-specific technologies including machine learning, molecular modeling, and bioinformatics. These techniques are complementary and can effectively predict the smallest possible changes that enhance the stability of such receptors and make it easier to obtain their molecular structure.”


This new approach, developed at MIPT, Skoltech, and USC, allows scientists to acquire the structure of four important human receptors, including cannabinoid receptors involved in brain signaling and pain perception, and prostaglandin receptors involved in the inflammatory process in humans. The results of studies on the structure of cannabinoid receptors and prostaglandin receptors are published in the journal Cell and Nature Chemical Biology, titled as “Crystal Structure of the Human Cannabinoid Receptor CB2” and “Crystal structure of misoprostol bound to the labor inducer”. Prostaglandin E2 receptor”.




Petr Popov et al, Computational design for thermostabilization of GPCRs, Current Opinion in Structural Biology (2019). DOI: 10.1016/

Xiaoting Li et al. Crystal Structure of the Human Cannabinoid Receptor CB2. Cell, 2019, doi:10.1016/j.cell.2018.12.011.

Martin Audet et al. Crystal structure of misoprostol bound to the labor inducer prostaglandin E2 receptor. Nature Chemical Biology, 2019, doi:10.1038/s41589-018-0160-y.



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