Beyond X-rays: an overview of emerging structural biology methods

Area of Science:

• Structural Biology
• Biophysics
• Biochemistry

Background:

• X-ray crystallography is the primary method for determining macromolecular structures.
• Emerging technologies are expanding the toolkit for structural biology.
• National facilities are enhancing support for novice researchers.

Purpose of the Study:

• To provide an overview of novel structural biology methods.
• To guide readers to in-depth literature on these techniques.
• To highlight advancements beyond traditional X-ray crystallography.

Main Methods:

• Serial femtosecond crystallography (SFX) using X-ray free electron lasers (XFELs) for time-resolved studies.
• Microcrystal electron diffraction (MicroED) to overcome crystal size limitations.
• Cryogenic electron microscopy (cryo-EM) for visualizing challenging macromolecules and complexes.

Main Results:

• XFELs and SFX enable time-resolved structure determination, capturing dynamic molecular processes.
• XFEL, SFX, and MicroED reduce the requirement for large crystals.
• Cryo-EM is revolutionizing the visualization of difficult-to-crystallize molecules at atomic resolution.

Conclusions:

• Novel methods like XFEL, SFX, MicroED, and cryo-EM are broadening structural biology capabilities.
• These techniques provide new avenues for understanding molecular structure and function.
• Advancements facilitate the study of dynamic processes and challenging biological targets.