In Silico Binding Affinities of the Molecules in Camellia Sinensis Teas to NLRP3 NACHT Domain

Year 2023, Volume: 12 Issue: 3, 910 - 917, 26.09.2023

Zekeriya Düzgün , Birgül Kural

https://doi.org/10.37989/gumussagbil.1273863

Abstract

NLRP3 inflammasome secretes proinflammatory cytokines in response to microbial infection and cellular damage, induces pyroptotic cell death, and triggers many pathological conditions. For this reason, it is important to determine the products that can inhibit the NLRP3 protein. In this study, the affinities of 27 molecules in Camellia sinensis tea species to ADP and inhibitor cavities in the NACHT domain of NLRP3 were analyzed in silico using molecular docking, molecular dynamics simulation, and free energy calculation method MM/GBSA. Among the components, theaflavic acid, (-)-epicatechin gallate and (-)-epigallocatechin gallate gave better binding affinities. It was concluded that it would be beneficial to conduct advanced studies on whether these three compounds contribute to the preventability of NLRP3-mediated inflammatory diseases.

Keywords

(-)-Epicatechin gallate, (-)-Epigallocatechin gallate, NLRP3, NACHT, Theaflavic acid

Thanks

The numerical calculations expressed in this paper were performed at TUBITAK ULAKBIM, High Performance, and Grid Computing Center (TRUBA resources).

Camellia Sinensis Çaylarındaki Moleküllerin NLRP3 NACHT Domainine İn Siliko Bağlanma Afiniteleri

Abstract

NLRP3 inflamazomu, mikrobiyal enfeksiyona ve hücresel hasara yanıt olarak proinflamatuar sitokinleri salgılar, piroptotik hücre ölümüne neden olur ve birçok patolojik durumu tetikler. Bu nedenle NLRP3 proteinini inhibe edebilen ürünlerin belirlenmesi önemlidir. Bu çalışmada, Camellia sinensis çay türünde bulunan 27 molekülün, NLRP3'ün NACHT domainindeki ADP ve inhibitör kavitelere afiniteleri, moleküler yerleştirme, moleküler dinamik simülasyonu ve serbest enerji hesaplama yöntemi MM/GBSA kullanılarak in siliko olarak analiz edildi. Bileşenler arasında tiflavik asit, (-)-epikateşin gallat ve (-)-epigallokateşin gallat daha iyi bağlanma afiniteleri verdi. Bu üç bileşiğin NLRP3 aracılı inflamatuvar hastalıkların önlenebilirliğine katkı sağlayıp sağlamadığına yönelik ileri çalışmaların yapılmasının faydalı olacağı kanısına varıldı.

Keywords

(-)-Epicatechin gallate, (-)-Epigallocatechin gallate, NLRP3, NACHT, Theaflavic acid

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