Clashes

From Proteopedia

Revision as of 21:40, 6 November 2021

Clashes in protein models, also called steric clashes, occur when two non-bonded atoms are impossibly close to each other. This happens when the van der Waals radii of the atoms overlap; that is, when two atoms are occupying the same space. Clashes typically occur in lower resolution models due to the difficulties of obeying all chemical constraints while optimizing the fit of the model to the experimental data. Clashes are more common in X-ray crystallographic models with resolutions of 3.0 Å or worse, or in cryo-EM models. (NMR models generally lack clashes because they are forced to obey chemical constraints.)

Clashes Dictate Protein Secondary Structure

The prevalence of alpha helices and beta strands in the secondary structure of proteins results from the avoidance of clashes in the polypeptide chain, as embodied in the Ramachandran Principle. Interactive visualizations of clashes during rotations of bonds in polypeptide chains are available at Tutorial:Ramachandran principle and phi psi angles. Many other related tutorials and perspectives will be found at Dihedral/Index.

Clashes vs. Model Quality

The presence of too many clashes in a model calls into question its reliability. All models submitted to the Protein Data Bank (PDB) are analyzed by MolProbity, which adds hydrogen atoms (where absent). MolProbity then determines a clash score ("clashscore"), which is the number of clashes per 1,000 atoms (including hydrogens), and ranks it relative to other models of the same resolution. A clash is considered to occur when the van der Waals radii overlap by ≥ 0.4 Å^[1]. Each wwPDB entry has an extensive Validation Report^[2]. Here are a couple of examples:

• 6zx4, an X-ray model of resolution 0.96 Å, contains 5,850 atoms including hydrogens. 6 clashes were present with atomic overlaps in the range 0.41-0.49 Å. The clashscore is thus 6/5.8 = 1.0. This placed it in about the 90th percentile (90% of the compared models have more clashes) of 1,321 models with resolutions of 0.86-1.06 Å. Full Validation Report.

• 6ef8, a cryo-EM model of resolution 3.7 Å, contains 22,911 non-hydrogen atoms. MolProbity added 20,895 hydrogens for a total of 43,806 atoms. 558 clashes were present with atomic overlaps in the range 0.4 to 1.47 Å. The clashscore is thus 558/43.8 = 13. This placed it in about the 35th percentile (35% of the compared models have more clashes) among the clashscores for all cryo-EM models. Full Validation Report.

Visualization of Clashes

• MolProbity offers visualization of clashes in NGL Viewer. Caution: the percentile rank of the clashscore is based on very old reference data.
• Jmol offers visualization of clashes in its Validation Tools. Jmol obtains clash data from the wwPDB (see "load =xxxx/val" under Annotations).

See Also

• Tutorial:Ramachandran principle and phi psi angles
• Dihedral/Index which has links to many tutorials and resources about the Ramachandran principle, and phi and psi angles in proteins.
• Ramachandran Plot
• Quality assessment for molecular models
• Steric Effects in Wikipedia

Notes and References

1. ↑ Too-Close Contacts at the World Wide Protein Data Bank.
2. ↑ wwPDB Validation Reports.