Correcting cis-trans-transgressions in macromolecular structure models

Many macromolecular X-ray and cryo-EM structure models deposited in the PDB contain biologically relevant small molecule ligands with unsaturated fatty acid acyl chains, whose cis-trans stereochemistry is incorrect. The molecules are either not properly defined in their stereochemical restraint files, or the proper stereochemistry is neglected during model building. Often, the same molecules appear in deposited models in both isomeric configurations, one of which is almost always incorrect, and the use of the same moiety (HET) identifier and restraint files in model refinement is wrong. We present case studies of frequently occurring molecules and a compilation of identified cases of C-C=C-C cis-trans geometry in the deposited structure models. Full listings of cis/trans torsion angles are provided for models with commonly occurring molecules to assist identification and correction of cis-trans errors and prevent inadvertent use of incorrect models. Caveats for users, advice for modellers and suggestions for remediation efforts with a simple but effective restraint file modification are provided.

Automated summary

Many macromolecular structure models in the PDB contain biologically relevant small molecule ligands with incorrect cis-trans stereochemistry. The errors may stem from deficiencies in stereochemical restraint files or negligence during model building. Awareness, identification, and correction of these errors are crucial to prevent inadvertent use of incorrect models.