What is cryo-EM?
Cryo-electron microscopy (cryo-EM) is a revolutionary Nobel prize-winning technique in structural biology which provides atomic resolution three-dimensional maps of important proteins including membrane proteins, GPCRs, ribosomes, and complexes. In cryo-EM, a liquid sample is imaged in a transmission electron microscope (TEM) under cryogenic conditions. The resulting 2D projections of the sample are processed using complex 3D reconstruction algorithms to obtain a near-atomic resolution 3D map of the structure(s).
How is cryo-EM revolutionizing structural biology and drug discovery?
Structural information is key to understanding how proteins function and how to design effective drugs and therapies. Cryo-EM can solve multiple structural conformations simultaneously, including structures of target proteins with ligands bound, yielding key insights into protein function and mechanisms of action.
Compared with traditional structural biology techniques such as x-ray crystallography and NMR, cryo-EM provides a significantly higher probability of obtaining 3D structural information as it requires only small quantities of biological sample and eliminates the requirement for crystallization. Instead, high performance algorithms are used to extract information from large numbers of noisy 2D microscope images to compute 3D structures of target proteins in near-native states. Cryo-EM structures, even at intermediate resolutions, yield critical insights into target biology, binding pockets, and conformational changes induced by ligand binding.
Cryo-EM has already been used to: solve structures of important proteins, including those involved in regulating aging and cancer, drug receptors involved in treating epilepsy and anxiety; shed light on the mechanism of action of diseases such as malaria, the zika virus and HSV-1, which enhance the ability to design effective therapies; and, to better understand how existing drugs and drug receptors work.