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

Chenghua Shao; Sebastian Bittrich; Sijian Wang; Stephen K Burley

doi:10.1016/j.str.2022.08.004

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

Structure. 2022 Oct 6;30(10):1385-1394.e3. doi: 10.1016/j.str.2022.08.004. Epub 2022 Aug 31.

Authors

Chenghua Shao¹, Sebastian Bittrich², Sijian Wang³, Stephen K Burley⁴

Affiliations

¹ Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. Electronic address: [email protected].
² Research Collaboratory for Structural Bioinformatics Protein Data Bank, San Diego Supercomputer Center, University of California San Diego, La Jolla, CA 92093, USA.
³ Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Statistics, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
⁴ Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Research Collaboratory for Structural Bioinformatics Protein Data Bank, San Diego Supercomputer Center, University of California San Diego, La Jolla, CA 92093, USA; Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA; Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. Electronic address: [email protected].

Abstract

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.

Keywords: AlphaFold2; AlphaFoldDB; PDB; Protein Data Bank; RCSB PDB; RSCC; macromolecular structure quality; pLDDT; real-space correlation coefficient; structure confidence.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Amino Acids*
Databases, Protein
Humans
Macromolecular Substances
Myxovirus Resistance Proteins
Protein Conformation

Substances

Amino Acids
Macromolecular Substances
Myxovirus Resistance Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding