Table 2. Comparison of the Basic Structure Determination Methods.

	Atomic resolution possible?	Typical resolution ranges	Size ranges	Resolvable features	Limitations	Minimal amount of sample required	Dynamic information
X-ray diffraction	yes	1.5–4 Å	from short peptides to MDa complexes and icosahedral viruses	atoms, secondary, tertiary, and quaternary structure	requires crystals, stringent purity	100–500 μl of 5–30 mg ml−1	ordered versus disordered regions
Single-particle EM	no	negative stain limited to ∼20 Å; particles in ice, ∼10 Å	proteins >250 kD (negative stain); >400 kD (particles in ice)	domain organization	limited resolution	∼100 μl of 0.1 mg ml−1	can image multiple conformations from one sample
Electron diffraction	yes	1.5–7 Å	15–250 kD	atoms, secondary, tertiary, and quaternary structure	requires 2D crystals or helical tubes	∼100 μl of 1 mg ml−1	ordered versus disordered regions
SAXS	no	10–20 Å	10 kD to 0.6 MDa	domain organization	limited resolution	100 μl of 5–30 mg ml−1	no
NMR	Yes	1.5–3 Å for backbone atoms	limited to <∼40 kDa	atoms, secondary, tertiary, and quaternary structure	sample molecular weight	100–500 μl of 5–30 mg ml−1	atom-specific dynamics can be measured