Rare ring conformations in PDB: Facts or wishful thinking?

j 2024

Rare ring conformations in PDB: Facts or wishful thinking?

BUČEKOVÁ, Gabriela, Viktoriia DOSHCHENKO, Aliaksei CHARESHNEU, Jana PORUBSKÁ, Michal PAJTINKA et. al.

Basic information

Original name

Rare ring conformations in PDB: Facts or wishful thinking?

Authors

BUČEKOVÁ, Gabriela, Viktoriia DOSHCHENKO, Aliaksei CHARESHNEU, Jana PORUBSKÁ, Michal PAJTINKA, Michal OLEKSIK, Tomáš SVOBODA, Vladimír HORSKÝ and Radka SVOBODOVÁ

Edition

bioRxiv, 2024

Other information

Language

English

Type of outcome

Článek v odborném periodiku (nerecenzovaný)

Field of Study

10608 Biochemistry and molecular biology

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1101/2024.06.20.598822

Keywords in English

validation, ring conformation, ligand, X-ray crystallography, Protein Data Bank

Abstract

V originále

Protein structural data are highly valuable for research, and many significant results have been published on their basis. A key point for their credibility and applicability is their quality. An important facet of protein structure quality is the validation of ligands. Some aspects of ligand quality have already been validated by established quality metrics. However, validation of ring conformation has yet to be comprehensively performed despite rings strongly influencing the formation of the ligand’s scaffold and shape. Most rings form several conformations that differ in their stability. The most stable ones occur frequently in nature and should, therefore, be found in Protein Data Bank (PDB) structures. In this article, we examined which conformations of rings occur in PDB structures. Our analysis focused on conformations of all cyclopentane, cyclohexane, and benzene rings in the PDB. Specifically, we examined 123 264 rings of 24 763 distinct ligands, which instances occur in 44 022 protein structures. In general, we found that most of the rings (98.32 %) are in energetically favourable conformations. Surprisingly, the existence of most of the energetically unfavourable ring conformations (2 067 samples, 1.68 %) is not supported by experimental data. Only 291 unfavourable ring conformations (0.24 %) are backed by experimental data that are accurate enough to distinguish the conformation, which shows that the existence of energetically unfavourable ring conformations is rarely supported by structural or experimental evidence. Our results suggest that each occurrence of untypical ring conformation in the PDB may indicate a potential error and should be carefully analysed.

Links

LM2023055, research and development project

Name: Česká národní infrastruktura pro biologická data

Investor: Ministry of Education, Youth and Sports of the CR, ELIXIR-CZ: Czech National Infrastructure for Biological Data

Citovat

BUČEKOVÁ, Gabriela, Viktoriia DOSHCHENKO, Aliaksei CHARESHNEU, Jana PORUBSKÁ, Michal PAJTINKA, Michal OLEKSIK, Tomáš SVOBODA, Vladimír HORSKÝ and Radka SVOBODOVÁ. Rare ring conformations in PDB: Facts or wishful thinking? bioRxiv. 2024. Available from: https://dx.doi.org/10.1101/2024.06.20.598822.

@article{2421800,
   author = {Bučeková, Gabriela and Doshchenko, Viktoriia and Chareshneu, Aliaksei and Porubská, Jana and Pajtinka, Michal and Oleksik, Michal and Svoboda, Tomáš and Horský, Vladimír and Svobodová, Radka},
   doi = {http://dx.doi.org/10.1101/2024.06.20.598822},
   keywords = {validation, ring conformation, ligand, X-ray crystallography, Protein Data Bank},
   language = {eng},
   journal = {bioRxiv},
   title = {Rare ring conformations in PDB: Facts or wishful thinking?},
   url = {https://www.biorxiv.org/content/10.1101/2024.06.20.598822v1},
   year = {2024}
}

TY  - JFULL
ID  - 2421800
AU  - Bučeková, Gabriela - Doshchenko, Viktoriia - Chareshneu, Aliaksei - Porubská, Jana - Pajtinka, Michal - Oleksik, Michal - Svoboda, Tomáš - Horský, Vladimír - Svobodová, Radka
PY  - 2024
TI  - Rare ring conformations in PDB: Facts or wishful thinking?
JF  - bioRxiv
KW  - validation, ring conformation, ligand, X-ray crystallography, Protein Data Bank
UR  - https://www.biorxiv.org/content/10.1101/2024.06.20.598822v1
N2  - Protein structural data are highly valuable for research, and many significant results have been published on their basis. A key point for their credibility and applicability is their quality. An important facet of protein structure quality is the validation of ligands. Some aspects of ligand quality have already been validated by established quality metrics. However, validation of ring conformation has yet to be comprehensively performed despite rings strongly influencing the formation of the ligand’s scaffold and shape. Most rings form several conformations that differ in their stability. The most stable ones occur frequently in nature and should, therefore, be found in Protein Data Bank (PDB) structures. In this article, we examined which conformations of rings occur in PDB structures. Our analysis focused on conformations of all cyclopentane, cyclohexane, and benzene rings in the PDB. Specifically, we examined 123 264 rings of 24 763 distinct ligands, which instances occur in 44 022 protein structures. In general, we found that most of the rings (98.32 %) are in energetically favourable conformations. Surprisingly, the existence of most of the energetically unfavourable ring conformations (2 067 samples, 1.68 %) is not supported by experimental data. Only 291 unfavourable ring conformations (0.24 %) are backed by experimental data that are accurate enough to distinguish the conformation, which shows that the existence of energetically unfavourable ring conformations is rarely supported by structural or experimental evidence. Our results suggest that each occurrence of untypical ring conformation in the PDB may indicate a potential error and should be carefully analysed.
ER  -

BUČEKOVÁ, Gabriela, Viktoriia DOSHCHENKO, Aliaksei CHARESHNEU, Jana PORUBSKÁ, Michal PAJTINKA, Michal OLEKSIK, Tomáš SVOBODA, Vladimír HORSKÝ and Radka SVOBODOVÁ. Rare ring conformations in PDB: Facts or wishful thinking? \textit{bioRxiv}. 2024. Available from: https://dx.doi.org/10.1101/2024.06.20.598822.

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