More and more, researchers turn to cryo-electron microscopy (cryo-EM) to gain insights into the structure and function of small molecules in complex with their drug discovery targets. One promising area of drug discovery encompasses GPCR structure analysis, a family of receptors found in the cell membranes of humans and other organisms.
What are GPCRs?
GPCRs, or G protein coupled receptors, function like switches, relaying messages into a cell.
This function allows the detection of molecules outside the cell and activation of responses within the cell—thus making GPCRs an ideal drug target.
Challenges and advancements of GPCR structure analysis for drug discovery
Until recently, X-ray crystallography was the standard method for small molecule structure-based drug design.
While this technique revolutionized our understanding of many proteins, GPCRs are difficult to crystallize, limiting GPCR structure determination using this method.
Today, cryo-EM can be used for determining high-resolution structures on a routine basis and is increasingly indispensable as an enabling technology for this target class.
Using cryo-EM, scientists can visualize mechanistic underpinnings of how different stimuli translate to a range of cellular responses. This optimization of GPCR-targeted molecules enables pharmaceutical companies to develop more effective drugs with fewer side effects for chronic diseases including diabetes, asthma, Parkinson’s Disease, schizophrenia, depression and various types of cancers.
Cryo-EM collaboration to power structure-based drug design
To help increase access to cryo-EM and its role in drug discovery, we recently collaborated with four universities and other leading organizations to establish the ARC Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery in Australia.
The ARC Training Centre is part of the Australian Government’s Industrial Transformation Training Centres (ITTC) program that fosters partnerships researchers “to provide innovative Higher Degree by Research and postdoctoral training, for end-user focused research industries that are vital to Australia’s future.”
The vision is to provide a highly skilled workforce that is proficient in industrial cryo-EM of membrane proteins.
These graduates will help shape the future of structure-enhanced drug design and make significant contributions to the discovery of urgently needed medicines.
Aleksander Stefanovic is a Senior Market Development Manager at Thermo Fisher Scientific.
Visit our Cryo-EM in the Pharmaceutical Industry webpage to learn more about how other pharmaceutical companies are using cryo-EM to accelerate their drug discovery.
To find out more about incorporating cryo-EM into drug discovery efforts, visit our Bio-pharmaceutical Research with Electron Microscopy page.
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