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Biophysical modeling indicates a high affinity of ethyl esters of omega-3 polyunsaturated fatty acids to the enzymes of the pro-inflammatory arachidonic acid cascade

https://doi.org/10.17749/2070-4909/farmakoekonomika.2022.142

Abstract

Background. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are widely used in modern cardiology. The anti-inflammatory effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is realized, in particular, by modulating the activity of the arachidonic acid (ARA) cascade.

Objective: to conduct biophysical analysis of the interactions of various forms of PUFAs (ARA, EPA, DHA, EPA and DHA ethyl esters) with three target proteins-enzymes of the ARA cascade (cyclooxygenase-1 (COX-1), COX-2, 5-lipoxygenase (5-LPOG)).

Material and methods. The minimization of the energy of the ligand-receptor complexes at various initial positions of the molecule relative to the receptor pocket and the molecular energy profiles of the protein (the energy of side chain transfer from solvent to protein) were calculated using the ECMMS package.

Results. EPA and DHA ethyl esters were characterized by significantly higher absolute values of specific binding energies of target proteins than ARA or simply EPA/DHA. For example, in the case of COX-2, EPA, DHA and EPA ethyl ester had similar ∆∆G values (–3.0...–3.1 kcal/mol), while the COX-2 complex with DHA ethyl ester was somewhat more stable (∆∆G = –3.4 kcal/mol). In the case of the 5-LPOG enzyme, the complex with EPA ethyl ester was the most stable (∆∆G = –1.62 kcal/mol). Higher absolute binding energies indicate a higher affinity of EPA and DHA ethyl esters to enzymes of the ARA cascade.

Conclusion. The results suggest that the high affinity of EPA and DHA ethyl esters to the enzymes of the ARA cascade is one of the molecular bases of therapeutic efficacy of ω-3 PUFAs with high degree of standardization.

About the Authors

I. Yu. Torshin
Federal Research Center “Informatics and Management”, Russian Academy of Sciences
Russian Federation

Ivan Yu. Torshin – PhD (Phys. Math.), PhD (Chem.), Senior Researcher, Institute of Pharmacoinformatics. WoS ResearcherID: C-7683-2018; Scopus Author ID: 7003300274; RSCI SPIN-code: 1375-1114

44 corp. 2 Vavilov Str., Moscow 2119333



O. A. Gromova
Federal Research Center “Informatics and Management”, Russian Academy of Sciences
Russian Federation

Olga A. Gromova – Dr. Med. Sc., Professor, Research Supervisor, Institute of Pharmacoinformatics. WoS ResearcherID: J-4946-2017; Scopus Author ID: 7003589812; RSCI SPIN-code: 6317-9833

44 corp. 2 Vavilov Str., Moscow 2119333



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Review

For citations:


Torshin I.Yu., Gromova O.A. Biophysical modeling indicates a high affinity of ethyl esters of omega-3 polyunsaturated fatty acids to the enzymes of the pro-inflammatory arachidonic acid cascade. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2022;15(2):221-229. (In Russ.) https://doi.org/10.17749/2070-4909/farmakoekonomika.2022.142

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