Hidden Pathways on the Surface of Cells

An international team of scientists has discovered new hidden pathways on the surface of cells that could change how drugs work in the body – and open the door to more precise and effective treatments for a wide range of diseases.

The discovery centers on special proteins called G protein-coupled receptors (GPCRs), which sit on the surface of cells and detect external molecules to activate an appropriate response. More than a third of all medicines approved by the FDA work by targeting GPCRs. However, until now, scientists didn’t fully understand all the ways drugs could interact with them.

With advances in computer simulations, the research team was able to look at these proteins in incredible detail – even at the atomic level – and watch how they interact with cell membranes. They identified hidden “gateways” in the GPCRs that could allow drugs to slip in and change how the proteins behave, potentially offering new ways to control how cells function.

Jana Selent, who led the study and coordinates the GPCR Drug Discovery Research Group at the Hospital del Mar Research Institute in Barcelona, said, “We have discovered new gateways for drugs to modulate proteins that regulate cellular activity. Having detailed information about the specific site where these drugs act within the cell will accelerate the development of targeted therapies.”

The study involved research centers from 13 countries, including Spain, the UK, Germany, France, Poland, the Netherlands, Denmark, the US, and China. 

The simulation data has been made available publicly, with the researchers hoping that the discovery could lead to more targeted therapies with fewer side effects, since drugs could be designed to fit more precisely into these newly found gateways. 

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