Aligning experimental and theoretical anisotropic B-factors: water models, normal-mode analysis methods, and metrics

Area of Science:

• Structural Biology
• Computational Biophysics
• Biochemistry

Background:

• X-ray crystallography provides insights into protein structure and dynamics.
• Anisotropic B-factors (ADPs) from high-resolution data are crucial for understanding protein dynamics, structure-function relationships.

Purpose of the Study:

• To evaluate metrics for comparing ellipsoidal overlaps.
• To apply normal-mode analysis (NMA) for predicting theoretical ADPs and aligning them with experimental results.
• To investigate the impact of explicit water on protein surface on ADP prediction accuracy.

Main Methods:

• In-depth evaluation of metrics for comparing ellipsoidal overlaps.
• Normal-mode analysis (NMA) to predict theoretical anisotropic B-factors (ADPs).
• Comparison of experimental and theoretical ADPs focusing on shape overlap, dominant direction alignment, and magnitude similarity.

Main Results:

• Explicitly treated water on the protein surface significantly improved energy minimization and reproduced experimental ADP anisotropy.
• The choice of water molecules, NMA methods, and overlap evaluation metrics critically influenced the results.
• Successful alignment of theoretical ADPs with experimental data was achieved.

Conclusions:

• Experimental ADPs from X-ray crystallography offer valuable information on protein dynamics.
• This study enhances the understanding of the physical basis and application potential of experimental ADPs.
• Methodological choices in NMA and ADP comparison are critical for accurate dynamic insights.