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Recent Advances in Inflammation & Allergy Drug Discovery


ISSN (Print): 2772-2708
ISSN (Online): 2772-2716

Research Article

Molecular Docking and Dynamics Simulation Studies of a Dataset of NLRP3 Inflammasome Inhibitors

Author(s): Igor J. dos Santos Nascimento*, Thiago M. de Aquino and Edeildo F. da Silva-Júnior

Volume 15, Issue 2, 2021

Published on: 26 January, 2022

Page: [80 - 86] Pages: 7

DOI: 10.2174/2772270816666220126103909

Price: $65


Background: The organism’s defense against aggressive agents is performed by the innate immune system via activation of pattern-recognition receptors (PRRs). Initially, these agents are recognized by the immune system, resulting in the inflammatory response that activates the pathogen elimination and tissue repair. Inflammasomes are macromolecules related to the host’s response to endo or exogenous aggressive agents. Thus, inflammation mediated by inflammasomes plays an important role in the pathogenesis of diseases, such as neurodegenerative disorders, autoimmune diseases, and type 2 diabetes, justifying their attractiveness as drug targets. One of the most important tasks remains in the ATPase nucleotide-binding oligomerization domain nucleotide- binding domain leucine-rich repeat-containing receptors protein 3 (NLRP3), in which the blocking of its oligomerization is related to the functional inhibition of inflammasomes. Here, we performed molecular docking and dynamics simulations for NP3-146, an analog of MCC950, to obtain information about the complex stability and main interactions with amino acid residues from NLRP3.

Methods: By using the crystalized structure recently deposited in the protein data bank (7alv), molecular docking in GOLD software and molecular dynamics simulations in GROMACS software were performed to generate the RMSD RMSF, Rg, SASA, and H-bond plots.

Results: The results of RMSD, RMSF, Rg, SASA, and H-bond plots of both complexes confirmed the stability at the active site. Besides, the analyses of the most stable conformation showed that the main interactions are performed with Ala227, Ala228, Pro352, Ile411, Phe575, and Arg578 residues.

Conclusion: This report confirmed the stability of NP3-146, similar to the known inhibitor MCC950, providing useful information for designing NLRP3 inhibitors.

Keywords: Inflammasomes, NLRP3, molecular docking, molecular dynamics, anti-inflammatory drugs, active sites.

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