Homology modeling of mouse NLRP3 NACHT protein domain and molecular dynamics simulation of its ATP binding properties

Hien T. T. Lai (), Do Minh Ha, Duc Manh Nguyen () and Toan T. Nguyen
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Hien T. T. Lai: VNU Key Laboratory Multiscale Simulation of Complex Systems, VNU University of Science, Vietnam National University, Hanoi, 334 Nguyen Trai Street, Thanh Xuan, Hanoi 11416, Vietnam
Do Minh Ha: Faculty of Biology, VNU University of Science, Vietnam National University, Hanoi, Vietnam3The Key Laboratory of Enzyme and Protein Technology (KLEPT), VNU University of Science, Vietnam National University, Hanoi, 334 Nguyen Trai Street, Thanh Xuan, Hanoi 11416, Vietnam
Duc Manh Nguyen: Culham Center for Fusion Energy, United Kingdom Atomic Energy Authority, Abingdon, OX14 3DB, UK
Toan T. Nguyen: VNU Key Laboratory Multiscale Simulation of Complex Systems, VNU University of Science, Vietnam National University, Hanoi, 334 Nguyen Trai Street, Thanh Xuan, Hanoi 11416, Vietnam5Faculty of Physics, VNU University of Science, Vietnam National University, Hanoi, Vietnam

International Journal of Modern Physics C (IJMPC), 2020, vol. 31, issue 03, 1-11

Abstract: Gout is an extremely painful form of inflammatory arthritis, caused by the formation of monosodium urate (MSU) crystals in the joints. MSU crystals are one of the triggers for the activation of nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome (NACHT, LRR and PYD domains-containing protein), which in turn induces caspase-1 activation and a nonspecific immune responses that cause inflammation. Further structural studies and ligand designs are needed to block the interaction of NLRP3 with MSU or allow the interaction without activating caspase-1. This would facilitate the screening of new drugs for the treatment of gout. Using computational methods for homology modeling and molecular dynamics simulations, the structural model of mouse NLRP3 protein with its domains, three potential structural models were consistently constructed and tested to find the most stable structural model. Adenosine triphosphate (ATP) — an activator of NACHT (the central domain of mouse NLRP3 protein) — was docked and simulated. Ligand effects to activate as well as limit this protein were analyzed. This study provides insights to deeper understanding about gout development pathway via the NLRP3 protein.

Keywords: Mouse NLRP3 protein; gout; molecular dynamics simulation; ATP binding; homology modeling (search for similar items in EconPapers)
Date: 2020
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DOI: 10.1142/S0129183120500369

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