Review Article

Biophysical Approaches Facilitate Computational Drug Discovery for ATP-Binding Cassette Proteins

Table 2

Comparison of commonly used biophysical techniques.

Parameter Biophysical technique
X-ray crystallographyNMR spectroscopyCryo-EM

MW range of proteins2–3,000 kDa60–65 kDa for all-atom;
800–1,000 kDa with sparse labeling
2–3,000 kDa
Time requiredUp to several yearsUp to 1 yearA few months
Typical resolution range2–4 ÅN/A>4 Å
Membrane proteinsYYY
Protein dynamicsNYN
Recapitulates physiologyNY/NY
ArtifactsCrystallization artifacts, single conformationReflecting conformational averagingPossible sample preparation artifacts
Expertise requiredYYY
Major advantageStreamlined, high resolution informationProviding information on protein dynamicsFully functional macromolecular complexes
Major disadvantageRequiring stable protein crystal that diffracts wellRequiring high concentration sampleLow signal-to-noise ratio for proteins smaller than 300 kDa