Normal mode refinement: crystallographic refinement of protein dynamic structure. II. Application to human lysozyme

Area of Science:

• Structural biology
• Biophysics

Background:

• Understanding protein dynamics is crucial for function.
• X-ray crystallography provides static snapshots, often obscuring dynamic information.

Purpose of the Study:

• To determine the dynamic structure of human lysozyme using normal mode refinement.
• To differentiate internal protein dynamics from external factors like lattice disorder.

Main Methods:

• Normal mode refinement applied to X-ray crystal structure data (5.0–1.8 Å resolution).
• Analysis of diffraction data collected on an imaging plate.
• Distinguishing internal atomic fluctuations from external terms.

Main Results:

• Debye-Waller factors comprise anisotropic internal and isotropic external components.
• Internal fluctuations, though smaller, exhibit similar features to normal mode analysis predictions.
• Correlated motions observed in the active site cleft, indicative of hinge-bending.

Conclusions:

• Internal protein dynamics are not directly apparent from electron density distributions.
• Normal mode refinement effectively captures anisotropic and concerted atomic fluctuations.
• The study elucidates the hinge-bending motion mechanism in human lysozyme.