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bioRxiv · 10.1101/2024.03.22.586129

Characterizing the Binding Mechanism of Sparsentan to the Type-2 Angiotensin II Receptor Using AutoDock Vina

Geng, P. X.
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Abstract

The angiotensin II type-2 receptor (AT2R) is known to have a significant impact on cardiovascular physiology, and the elucidation of its drug interactions is crucial for advancing therapeutic interventions. Sparsentan is an antagonist of angiotensin II, which has received FDA approval due to its demonstrated efficacy in ameliorating proteinuria. While sparsentan exhibits a preferential affinity for angiotensin II type-1 receptor (AT1R) and may primarily target it, DrugBank identifies it as a drug that targets AT2R. Present databases lack detailed structural data on the interaction mechanism between sparsentan and AT2R, leaving no definitive evidence to confirm or refute an interaction with AT2R. This study aimed to explore the potential for an interaction between sparsentan and AT2R. Molecular docking simulations were conducted using AutoDock Vina to predict the binding conformation. The docking parameters were meticulously optimized to ensure the accuracy and reliability of the simulation results. Subsequently, the most stable sparsentan-AT2R complex was determined. We identified four primary types of interactions at the binding site containing hydrogen bonds, hydrophobic interactions, {pi}-cation interactions, and {pi}-stacking, that are likely to contribute to the affinity of sparsentan for AT2R. Our study indicates that sparsentan may potentially interact with AT2R, our results may serve as a valuable reference for elucidating the mechanism of sparsentan action and for guiding the design of AT2R-targeted drugs.

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Geng, P. X.. 2024-03-27. Characterizing the Binding Mechanism of Sparsentan to the Type-2 Angiotensin II Receptor Using AutoDock Vina. https://doi.org/10.1101/2024.03.22.586129

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