Steroid hormone binding and modulation of Trichinella spiralis progesterone receptor: A computational approach

类固醇激素与旋毛虫孕酮受体的结合和调节:一种计算方法

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Abstract

Trichinellosis, caused by Trichinella species, including Trichinella spiralis, is a foodborne zoonotic disease. Upon ingestion, ML swiftly invade the intra-multicellular niche of the small intestine, undergoing four rapid molts to mature into adults. In general, the route of transmission for T. spiralis nematodes occurs through ingestion of pork. Therefore, it is crucial to develop a vaccine that can deal with trichinellosis, particularly for humans and pigs. In this study, homology modelling, molecular docking, simulations and molecular mechanics-based scoring (MM/GBSA) are used to investigate the interaction between T. spiralis membrane-associated progesterone receptor component 2 (Ts-MAPRC2) and different steroids hormones. In the most favorable region, 93 amino acid residues (92.1 %) are located, while 7 amino acids (6.9 %) are located in the allowed region, showing that the model with a 93.33 ERRAT quality factor is good quality. The MD simulations were conducted for 50 ns to explore the affinities and stability of four hormones chosen from the docking studies that showed similar binding poses to the control hormone Mifepristone. Simulations showed that the selected hormones were potent Ts-MAPRC2 binders and can act as leads to determine their activity by biophysical assays. Discovery of these five steroid hormones and interactions with Ts-MAPRC2 could lead to new therapies and vaccines for trichinellosis.

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