All-atom modeling of anisotropic atomic fluctuations in protein crystal structures

Area of Science:

• Structural biology
• Computational biophysics
• X-ray crystallography

Background:

• Accurate modeling of protein dynamics in crystalline states is crucial for computational simulations under physiological conditions.
• Previous coarse-grained modeling of atomic fluctuations in protein crystals has been refined.

Purpose of the Study:

• To refine protein dynamics modeling using all-atom representation and force fields.
• To assess the impact of crystalline environments (explicit and implicit) on protein dynamics.
• To compare modeling accuracy with experimental anisotropic displacement parameters (ADP).

Main Methods:

• Calculated anisotropic atomic fluctuations of protein structures.
• Modeled protein-environment interactions explicitly (neighboring proteins) and implicitly (harmonic restraints).
• Compared computational results with experimental ADPs from X-ray crystallography for 40 protein structures.

Main Results:

• Optimal modeling of ADPs occurred when protein-environment interactions were weaker than internal protein interactions.
• Crystal packing was found to only weakly perturb the intrinsic dynamics of protein structures.
• All-atom representation did not yield noticeable improvement over coarse-grained models for ADP accuracy.

Conclusions:

• Intrinsic protein dynamics are largely preserved despite crystal packing.
• Coarse-grained modeling offers both efficiency and accuracy for investigating protein dynamics.
• The findings justify the continued use of coarse-grained approaches in structural biology.