Assessing PDB Macromolecular Crystal Structure Confidence at the Individual Amino Acid Residue Level

Abstract

Approximately 87% of the more than 190,000 atomic-level, (three-dimensional) 3D biostructures in the Protein Data Bank (PDB) were determined using macromolecular crystallography (MX). Agreement between 3D atomic coordinates and experimental data for >100 million individual amino acid residues occurring within [~]150,000 PDB MX structures was analyzed in detail. The Real-Space-Correlation-Coefficient (RSCC) calculated using the 3D atomic coordinates for each residue and experimental electron density enables outlier detection of unreliable atomic coordinates (particularly important for poorly-resolved sidechain atoms) and ready evaluation of local structure quality by PDB users. For human protein MX structures in PDB, comparisons of per-residue RSCC experimental-agreement metric with AlphaFold2 computed structure model confidence (pLDDT-predicted local distance difference test) document (i) that RSCC values and pLDDT scores are correlated (median correlation coefficient[~]0.41), and (ii) that experimentally-determined MX structures (3.5 [A] resolution or better) are more reliable than AlphaFold2 computed structure models and should be used preferentially whenever possible.