Simplified quality assessment for small-molecule ligands in the Protein Data Bank

Chenghua Shao; John D Westbrook; Changpeng Lu; Charmi Bhikadiya; Ezra Peisach; Jasmine Y Young; Jose M Duarte; Robert Lowe; Sijian Wang; Yana Rose; Zukang Feng; Stephen K Burley

doi:10.1016/j.str.2021.10.003

Simplified quality assessment for small-molecule ligands in the Protein Data Bank

Structure. 2022 Feb 3;30(2):252-262.e4. doi: 10.1016/j.str.2021.10.003. Epub 2022 Jan 12.

Authors

Affiliations

¹ Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, 174 Frelinghuysen Road, Piscataway, NJ 08854, USA. Electronic address: chenghua.shao@rcsb.org.
² Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, 174 Frelinghuysen Road, Piscataway, NJ 08854, USA.
³ Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, 174 Frelinghuysen Road, Piscataway, NJ 08854, USA.
⁴ Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
⁵ Research Collaboratory for Structural Bioinformatics Protein Data Bank, San Diego Supercomputer Center, University of California San Diego, La Jolla, CA 92093, USA.
⁶ Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, 174 Frelinghuysen Road, Piscataway, NJ 08854, USA; Department of Statistics and Biostatistics, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
⁷ Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, 174 Frelinghuysen Road, Piscataway, NJ 08854, USA; Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA; Research Collaboratory for Structural Bioinformatics Protein Data Bank, San Diego Supercomputer Center, University of California San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA; Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. Electronic address: stephen.burley@rcsb.org.

Abstract

More than 70% of the experimentally determined macromolecular structures in the Protein Data Bank (PDB) contain small-molecule ligands. Quality indicators of ∼643,000 ligands present in ∼106,000 PDB X-ray crystal structures have been analyzed. Ligand quality varies greatly with regard to goodness of fit between ligand structure and experimental data, deviations in bond lengths and angles from known chemical structures, and inappropriate interatomic clashes between the ligand and its surroundings. Based on principal component analysis, correlated quality indicators of ligand structure have been aggregated into two largely orthogonal composite indicators measuring goodness of fit to experimental data and deviation from ideal chemical structure. Ranking of the composite quality indicators across the PDB archive enabled construction of uniformly distributed composite ranking score. This score is implemented at RCSB.org to compare chemically identical ligands in distinct PDB structures with easy-to-interpret two-dimensional ligand quality plots, allowing PDB users to quickly assess ligand structure quality and select the best exemplars.

Keywords: PDB; Protein Data Bank; RCSB PDB; composite ranking score; ligand quality indicator; ligand structure; ligand structure quality; multivariate analysis; principal component analysis; small-molecule ligand.

Publication types

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

MeSH terms

Databases, Protein
Ligands
Models, Molecular
Protein Conformation
Proteins / chemistry*
Proteins / metabolism*
Small Molecule Libraries / pharmacology*

Substances

Ligands
Proteins
Small Molecule Libraries

Grants and funding

R01 GM133198/GM/NIGMS NIH HHS/United States