Programme

P.11 -- Poster, NCTP-43

Date: Tuesday, 31 July 2018

Time: 08:30 - 10:00

Conformational analysis of mouse NLRP3 domain structures by molecular dynamics simulation

Lai Thi Thu Hien (1), Le Hoang Phong (1), Nguyen The Toan (1), Do Minh Ha (2)

(1) VNU Key Laboratory “Multiscale Simulation of Complex Systems”, VNU University of Science, 334 Nguyen Trai, Thanh Xuan, Hanoi, VIETNAM (2) Proteomics and Structural Biology Unit, KLEPT, VNU University of Science, 334 Nguyen Trai, Thanh Xuan, Hanoi, VIETNAM

Gout is an extremely painful form of inflammatory arthritis caused by the formation of urate crystals (MSU) in the joints. While the MSU crystal is one of the triggers for NLRP3 inflammasome (NACHT, LRR and PYD domains-containing protein 3), it induces caspase-1 activation, and non-specific immune responses that cause inflammation. Therefore, structural studies and ligand designs for NLRP3 to make this protein unable to combine with MSU or combine without activation are necessary for Gout treatment. Using computational methods for comparative modeling and molecular dynamics simulations, the structure of NLRP3 protein with its domains, 3 potential structures are consistently constructed and tested. Next, the activator (Adenosine triphosphate - ATP) to NACHT and ASC with NLRP3 structures are docked and simulated. Ligands effect to action as well as limit of this protein is analyzed. This provide insights to understanding Gout disease development pathway via NLRP3 protein. Keywords: Molecular dynamic simulation, NLRP3 inflammasome, MSU, Gout treatment, ligand docking, ATP, ASC.

Presenter: Lai Thi Thu Hien