Atomic model validation using the CCP-EM software suite.

Area of Science:

• Structural Biology
• Biophysics
• Computational Biology

Background:

• Cryo-electron microscopy (cryo-EM) has advanced significantly, leading to more atomic models.
• Variable local resolution and resolutions worse than 3 Å are common challenges.
• Atomic model validation is critical for identifying unreliable regions in cryo-EM structures.

Purpose of the Study:

• To present a graphical user interface for atomic model validation within the CCP-EM software suite.
• To create a platform for accessing multiple complementary validation metrics.
• To provide a summary of evaluations for cryo-EM atomic models.

Main Methods:

• Implementation of a graphical user interface for atomic model validation in CCP-EM.
• Utilizing multiple complementary validation metrics across various resolutions.
• Analysis of atomic models from SARS-CoV-2 cryo-EM structures.

Main Results:

• Models often favor common conformations over fitting observed data at lower resolutions.
• Stereochemical quality may be prioritized over data fit at low resolutions.
• Re-refinement can improve data agreement without compromising geometric quality.

Conclusions:

• Care must be taken to ensure low-resolution models accurately reflect observable data features.
• Improved resolution-dependent weight optimization in refinement is needed.
• An effective overfitting test is essential for guiding cryo-EM model refinement.