Assessing PDB macromolecular crystal structure confidence at the individual amino acid residue level

Approximately 87% of the more than 190,000 atomic-level three-dimensional (3D) biostructures in the 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-data-derived electron density enables outlier detection of unreliable atomic coordinates (particularly important for poorly resolved side-chain atoms) and ready evaluation of local structure quality by PDB users. For human protein MX structures in PDB, comparisons of the per-residue RSCC metric with AlphaFold2-computed structure model confidence (pLDDT-predicted local distance difference test) document (1) that RSCC values and pLDDT scores are correlated (median correlation coefficient ∼0.41), and (2) that experimentally determined MX structures (3.5 Å resolution or better) are more reliable than AlphaFold2-computed structure models and should be used preferentially whenever possible. [Display omitted] •Per-residue confidence of PDB crystal structures was evaluated by RSCC•RSCC values are correlated with AlphaFold2-computed structure model pLDDT scores•Crystal structures in PDB are generally more reliable than AlphaFold2 models•PDB crystal structure quality displayed using color scheme similar to AlphaFoldDB Shao et al. analyze crystal structure per-residue quality using the real-space correlation coefficient (RSCC) and identified outliers rigorously. Per-residue RSCC values are correlated with the AlphaFold2-computed structure model per-residue prediction confidence. PDB crystal structures are generally more reliable than AlphaFold2 models, and per-residue quality is displayed using a color scheme like AlphaFoldDB.