Perspectives and expectations in structural bioinformatics of metalloproteins

Abstract

Recent papers highlight the presence of large numbers of compressed angles in metal ion coordination geometries for metalloprotein entries in the worldwide Protein Data Bank, due mainly to multidentate coordination. The prevalence of these compressed angles has raised the controversial idea that significantly populated aberrant or even novel coordination geometries may exist. Some of these papers have undergone severe criticism, apparently due to views held that only canonical coordination geometries exist in significant numbers. While criticism of controversial ideas is warranted and to be expected, we believe that a line was crossed where unfair criticism was put forth to discredit an inconvenient result that compressed angles exist in large numbers, which does not support the dogmatic canonical coordination geometry view. We present a review of the major controversial results and their criticisms, pointing out both good suggestions that have been incorporated in new analyses, but also unfair criticism that was put forth to support a particular view. We also suggest that better science is enabled through: i) a more collegial and collaborative approach in future critical reviews and ii) the requirement for a description of methods and data including source code and visualizations that enables full reproducibility of results.

Finding High-Quality Metal Ion-Centric Regions Across the Worldwide Protein Data Bank

“…Therefore, the maximum electron density discrepancy criterion was derived from the metal ion electron discrepancy distribution itself (i.e., one standard deviation representing 19.3e). For commonly bound metal ions, additional criteria can be used for quality control [13], including the evaluation of bond lengths between ligating atoms (using the coordination chemistry definition of ligand) and the metal ion and coordination shell considerations [8,29,32]. However, several of these evaluations require the accurate identification of ligating atoms and are complicated by the wide variation in coordination geometries.…”

Finding high-quality metal ion-centric regions across the worldwide Protein Data Bank

“…The other criteria include electron density resolution, exclusion of nearby symmetry atoms, and the occupancy of the metal ion. For commonly-bound metal ions, additional criteria can be used for quality control [13], including the evaluation of bond lengths between ligating atoms (using the coordination chemistry definition of ligand) and the metal ion and coordination shell considerations [8,23,24]. However, several of these evaluations require the accurate identification of ligating atoms and is complicated by the wide variation in coordination geometries.…”

Aberrant coordination geometries discovered in the most abundant metalloproteins

“…These constraints, mostly in the form of bidentated ligands, and associated aberrant CGs included unique functional relationships. These controversial results generated criticism that we address in a companion perspective article . Also, these results created several new questions: Could similar functionally‐relevant structural descriptions of CG be constructed for other common metals, involving different numbers of ligands? Would similar or even new structural constraints and aberrant CGs be detected? …”

“…These controversial results generated criticism 18 that we address in a companion perspective article. 19 Also, these results created several new questions:…”