Prior knowledge or freedom of interpretation? A critical look at a recently published classification of “novel” Zn binding sites

Raczynska, J.E.; Wlodawer, Alexander; Jaskólski, Mariusz

doi:10.1002/prot.25024

Cited by 16 publications

(24 citation statements)

References 15 publications

(21 reference statements)

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“…That is, in PDB‐REDO, differences between models are more likely to be true differences instead of refinement‐related inconsistencies and the models are therefore more informative Moreover, using a higher‐quality structure data resource may prevent incorrect conclusions from dubious data. For example, a recent study detected a number of “novel zinc coordination geometries,” most, if not all, of which were simply errors in the input PDB data …”

Section: Discussionmentioning

confidence: 99%

“…For example, a recent study 36 detected a number of "novel zinc coordination geometries," most, if not all, of which were simply errors in the input PDB data. 37 Importantly, H-bond restraints are aimed at improving the geometry of protein structure models and are therefore not solely applicable to models solved by X-ray crystallography, but also to models obtained from cryo-EM. Models solved by cryo-EM still have a relatively low resolution compared to X-ray crystallography and often have homologous domains of higher resolution present in the PDB.…”

Section: Discussionmentioning

confidence: 99%

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Homology‐based hydrogen bond information improves crystallographic structures in the PDB

et al. 2017

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The Protein Data Bank (PDB) is the global archive for structural information on macromolecules, and a popular resource for researchers, teachers, and students, amassing more than one million unique users each year. Crystallographic structure models in the PDB (more than 100,000 entries) are optimized against the crystal diffraction data and geometrical restraints. This process of crystallographic refinement typically ignored hydrogen bond (H‐bond) distances as a source of information. However, H‐bond restraints can improve structures at low resolution where diffraction data are limited. To improve low‐resolution structure refinement, we present methods for deriving H‐bond information either globally from well‐refined high‐resolution structures from the PDB‐REDO databank, or specifically from on‐the‐fly constructed sets of homologous high‐resolution structures. Refinement incorporating HOmology DErived Restraints (HODER), improves geometrical quality and the fit to the diffraction data for many low‐resolution structures. To make these improvements readily available to the general public, we applied our new algorithms to all crystallographic structures in the PDB: using massively parallel computing, we constructed a new instance of the PDB‐REDO databank (https://pdb-redo.eu). This resource is useful for researchers to gain insight on individual structures, on specific protein families (as we demonstrate with examples), and on general features of protein structure using data mining approaches on a uniformly treated dataset.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Homology‐based hydrogen bond information improves crystallographic structures in the PDB

et al. 2017

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“…Relevant materials and methods are described in Yao et al 2015, 2017and Raczynska et al 2016. These statements are patently false, because while our previous article 2 was under peer review, we uploaded a 68 megabyte gzipped tar file (tarball) to our website containing all of the code used and the results from the article as shown in Figure 1 December 7, 2015 (the webpage says December 15, but our timestamps indicate it was actually December 7) to remove improvements in the algorithm not reflected in the published material.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, Raczynska, Wlodawer, and Jaskolski published the research article “Prior knowledge or freedom of interpretation? A critical look at a recently published classification of “novel” Zn binding sites,” a “critique” of our previously published article “A less‐biased analysis of metalloproteins reveals novel zinc coordination geometries …”

Section: Introductionmentioning

confidence: 99%

Perspectives and expectations in structural bioinformatics of metalloproteins

Yao

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et al. 2017

Proteins

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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.

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“…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? …”

Section: Introductionmentioning

confidence: 99%

Aberrant coordination geometries discovered in the most abundant metalloproteins

et al. 2017

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Metalloproteins bind and utilize metal ions for a variety of biological purposes. Due to the ubiquity of metalloprotein involvement throughout these processes across all domains of life, how proteins coordinate metal ions for different biochemical functions is of great relevance to understanding the implementation of these biological processes. Towards these ends, we have improved our methodology for structurally and functionally characterizing metal binding sites in metalloproteins. Our new ligand detection method is statistically much more robust, producing estimated false positive and false negative rates of ~0.11% and ~1.2%, respectively. Additional improvements expand both the range of metal ions and their coordination number that can be effectively analyzed. Also, the inclusion of additional quality control filters has significantly improved structure-function Spearman correlations as demonstrated by rho values greater than 0.90 for several metal coordination analyses and even one rho value above 0.95. Also, improvements in bond-length distributions have revealed bond-length modes specific to chemical functional groups involved in multidentation. Using these improved methods, we analyzed all single metal ion binding sites with Zn, Mg, Ca, Fe, and Na ions in the wwPDB, producing statistically rigorous results supporting the existence of both a significant number of unexpected compressed angles and subsequent aberrant metal ion coordination geometries (CGs) within structurally known metalloproteins. By recognizing these aberrant CGs in our clustering analyses, high correlations are achieved between structural and functional descriptions of metal ion coordination. Moreover, distinct biochemical functions are associated with aberrant CGs versus non-aberrant CGs.

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Prior knowledge or freedom of interpretation? A critical look at a recently published classification of “novel” Zn binding sites

Cited by 16 publications

References 15 publications

Homology‐based hydrogen bond information improves crystallographic structures in the PDB

Homology‐based hydrogen bond information improves crystallographic structures in the PDB

Perspectives and expectations in structural bioinformatics of metalloproteins

Aberrant coordination geometries discovered in the most abundant metalloproteins

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