Sharper Images of Molecules Using Cryo-Electron Microscopy
The molecular structure of numerous proteins cannot be determined using standard methods such as X-ray crystallography. New methods to determine protein structures are needed.
IRP researchers led by Sriram Subramaniam, Ph.D., developed groundbreaking new technology based on cryo-electron microscopy (cryo-EM) to determine the atomic structures of proteins. They have achieved resolutions which are comparable to X-ray crystallography, including on small proteins.
As new structures unfold at near-atomic resolution, the implications for drug discovery and development are revolutionary. Cryo-EM maps showing the contacts between small molecules and proteins will help explore questions such as why one drug is better than another or why certain drugs fail.
Bartesaghi A, Merk A, Banerjee S, Matthies D, Wu X, Milne JL, Subramaniam S. (2015). 2.2 Å resolution cryo-EM structure of β-galactosidase in complex with a cell-permeant inhibitor. Science. 348(6239):1147-51.
Banerjee S, Bartesaghi A, Merk A, Rao P, Bulfer SL, Yan Y, Green N, Mroczkowski B, Neitz RJ, Wipf P, Falconieri V, Deshaies RJ, Milne JL, Huryn D, Arkin M, Subramaniam S. (2016). 2.3 Å resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition. Science. 351(6275):871-5.