3rd International Conference on Chemo and BioInformatics, Kragujevac, September 25-26. 2025. (pp. 608-611)
АУТОР(И) / AUTHOR(S): Yaraslau U. Dzichenka, Natalia E. Boboriko, Sergey A. Usanov, Suzana Jovanović-Šanta, Biljana Šmit
Download Full Pdf 
DOI: 10.46793/ICCBIKG25.608D
САЖЕТАК / ABSTRACT:
Statistical analysis of 6,859 intermolecular contacts in experimentally determined spatial structures of cytochromes P450 (CYPs) with ligands, stored in the Protein Data Bank (PDB), was performed. The most frequent types of contacts are hydrophobic interactions, hydrogen bonds, water bridges, and π-stacking interactions. Domain-specific analysis of the interaction types allowed identifying of interaction patterns, which are specific for bacterial and eukaryotic proteins. Among these patterns amino acids (AA) involved in ligand binding are preferred. The high fraction of hydrophobic contacts reflects the fact that many of the tested ligands are lead compounds and that the active site of most CYPs is more hydrophobic than hydrophilic. The results highlight cytochromes P450 specific ligand-binding peculiarities, which are of great importance for molecular structure embedding in deep learning neural networks and for the development of efficient scoring functions to analyze molecular docking results.
КЉУЧНЕ РЕЧИ / KEYWORDS:
cytochrome P450, intermolecular interaction, Protein Data Bank, ligand
ПРОЈЕКАТ / ACKNOWLEDGEMENT:
This research was partially funded by the Belarusian Republican Foundation for Fundamental Research (Grant No. X25MC-012), Belarus-Serbia bilateral projects (X18SRBG- 002/51-03-003036/2017-09/02 and X20SRBG-004/337-00-00612/2019-09/04) and the Ministry of science, technological development and innovation of the Republic of Serbia (Contract No. 451-03-136/2025-03/200378).
ЛИТЕРАТУРА / REFERENCES:
- J. D. Finnigan, C. Young, D.J. Cook, S.J. Charnock, G.W. Black., Chapter Nine – Cytochromes P450 (P450s): A review of the class system with a focus on prokaryotic P450s, Adv. Protein Chem. Struct. Biol., 122 (2020) 289-320.
- S. L. Kelly, D.E. Kelly., Microbial cytochromes P450: biodiversity and biotechnology. Where do cytochromes P450 come from, what do they do and what can they do for us?, Philos. Trans. R. Soc. B, Biol. Sci., 2013 (19) 20120476.
- V. B. Urlacher, M. Girhard., Cytochrome P450 monooxygenases: an update on perspectives for synthetic application, Trends Biotech., 30 (2012) 26-36.
- D. C. Lamb, M.R. Waterman., Unusual properties of the cytochrome P450 superfamily, Philos. Trans. R. Soc. B, Biol. Sci., 368 (2013) 20120434.
- D. Minerdi, S. Savoi, P. Sabbatini., Role of Cytochrome P450 Enzyme in Plant Microorganisms’ Communication: A Focus on Grapevine, Int. J. Mol. Sci. 24 (2023) 4695.
- B. Črešnar, Š. Petrič., Cytochrome P450 enzymes in the fungal kingdom, Biochim. Biophys. Acta – Proteins Proteom., 1814 (2011) 29-35.
- F. P. Guengerich, M.R. Waterman, M.Egli., Recent Structural Insights into Cytochrome P450 Function, Trends Pharmacol. Sci., 37 (2016) 625-640.
- M. F. Adasme, K.L. Linnemann, S.N. Bolz, F. Kaiser, S. Salentin, V.J. Haupt, M. Schroeder., PLIP 2021: expanding the scope of the protein–ligand interaction profiler to DNA and RNA, Nucleic Acids Res., 49 (2021) W530–W534.