Programme

P.61 -- Poster, VCTP-49

Date: Friday, 2 August 2024

Time: 08:30 - 10:00

Investigating the site-dependent thermal stability of G6PD by coarse-grained and all-atom simulations

Nhung T. T. Nguyen (1,2), Phuong Thuy Bui (3), Nguyen Thi Hai Yen (2) and Trinh X. Hoang (2)

(1) Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam; (2) Institute of Physics, Vietnam Academy of Science and Technology, 10 Dao Tan, Ba Dinh, Hanoi, Vietnam; (3) Institute of Theoretical and Applied Research, Duy Tan University, Hanoi 100000, Vietnam

The enzyme glucose-6-phosphate dehydrogenase (G6PD) plays an important role in protecting red blood cells against oxidative damage through the production of reductive NADPH. A reduced activity of G6PD can lead to red blood cell breakdown causing hemolytic anemia. G6PD deficiency, being the most commonly known enzymopathy, is genetically inherited affecting ~5% of the world population. The catalytic activity of G6PD has been shown experimentally to correlate with its thermal stability. By using molecular dynamics simulations with a coarse-grained structure-based model we have shown that residue positions (or sites) in the protein sequence that have the largest contributions to the protein’s specific heat are statistically linked to point mutations associated with G6PD deficiency. Here, we dwell further into this issue by doing all-atom simulations of the monomeric G6PD in water solution. We show that the site-dependent thermal stability in the coarse-grained model to a significant degree correlates with that in all-atom simulations.

Presenter: Nguyen Thi Thuy Nhung