X-ray Diffraction (XRD) has been an indispensable tool in material science, structural chemistry, and structural biology. Despite advancements in laboratory X-ray and synchrotron sources over the past few decades, a significant roadblock in determining molecular structures remains: the ability to grow crystals of sufficient size and quality. Crystal optimization can be time-consuming, complicated, and requires large amounts of purified molecules, often making it unfeasible for many biological macromolecules and pharmaceutical compounds.
Electron crystallography methods, such as 3D Electron Diffraction (3D ED) / MicroED and Serial Electron Diffraction (SerialED), have the potential to overcome these challenges by allowing the determination of structures from crystals that are one billionth the volume of those used for Single-Crystal X-ray Diffraction (SCXRD). Since 2007, 3D ED has enabled the structure determination of landmark samples, mostly inorganic, considered impracticable for X-ray methods. Researchers from several laboratories have developed various experimental setups for data acquisition, such as automated diffraction tomography (ADT, University of Mainz) and rotation electron diffraction (RED, Stockholm University). In 2013, Gonen’s lab successfully developed the MicroED technique for determining macromolecular crystal structures. More recently, SerialED was developed independently by researchers at the Max Planck Institute and Stockholm University. However, 3D ED / MicroED and SerialED are still in their infancy, and further development is needed to unleash their full potential in material science, structural chemistry, and structural biology.
At Crystal35, I will present our latest results and provide a future perspective on electron crystallography methods.