X-ray diffuse scattering and rigid-body motion in crystalline lysozyme probed by molecular dynamics simulation

Area of Science:

• Biophysics
• Structural Biology
• Computational Chemistry

Background:

• Understanding protein dynamics is crucial for deciphering biological function.
• X-ray diffuse scattering is sensitive to collective atomic motions within proteins.
• Molecular dynamics simulations provide atomic-level insights into protein flexibility.

Purpose of the Study:

• To identify rigid body motions in hen egg-white lysozyme using molecular dynamics.
• To assess the contribution of these rigid body motions to X-ray diffuse scattering.
• To develop a model for protein dynamics based on rigid body approximations.

Main Methods:

• 1 ns molecular dynamics simulation of orthorhombic hen egg-white lysozyme unit cell.
• Dynamical cluster technique applied to the intramolecular interatomic fluctuation matrix to identify rigid atomic groups.
• Calculation of X-ray diffuse scattering patterns from full simulation and rigid body trajectories.

Main Results:

• Rigid body motions were identified, primarily involving local backbone atom groups and disulfide bond-connected residues.
• A model where backbone atoms form rigid groups and side-chains act as separate rigid bodies accurately reproduced experimental X-ray diffuse scattering (R-factor of 5%).
• Treating secondary structural elements as rigid bodies yielded quantitatively poorer agreement with scattering data.

Conclusions:

• Collective protein motions, particularly those involving identified rigid body segments, are key determinants of X-ray diffuse scattering.
• A simplified model of protein dynamics, focusing on rigid backbone groups and side-chains, can effectively capture scattering phenomena.
• Rigid whole-molecule and domain motions have minimal impact on protein atom displacements relevant to diffuse scattering.