Glutathione Peroxidase from Talaromyces marneffei Interacts with Host Protein MOB1A: Insights from Molecular Dynamics Simulation

Talaromyces marneffei is an opportunistic intracellular fungal pathogen that survives within macrophages by adapting to oxidative stress. Glutathione peroxidase (TmGpx1) contributes to antioxidant defense; however, its potential role in host–pathogen interactions has never been investigated. In this study, a yeast two-hybrid assay identified several host partner proteins, including MOB1A (MOB Kinase Activator 1A), a scaffold protein in the Hippo signaling pathway. To support this interaction, computational molecular dynamics simulations were performed, and the predicted interface was benchmarked against the canonical NDR (nuclear Dbf2-related)–MOB1A complex. The TmGpx1–MOB1A complex formed a stable interaction throughout the simulation, as indicated by consistent minimum distances, contact numbers, hydrogen bonding, and buried surface areas. However, compared to the NDR–MOB1A complex, the TmGpx1 interaction exhibited fewer intermolecular contacts and hydrogen bonds, a smaller interfacial area, and weaker binding free energy, indicating a less optimized interaction. Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) analysis supported spontaneous binding for both complexes, with weaker binding for TmGpx1–MOB1A (ΔG, −56.18 ± 23.11 kcal/mol) compared with NDR–MOB1A (ΔG, −127.24 ± 35.60 kcal/mol). MOB1A maintained structural stability upon binding to TmGpx1. Although these results supported weaker MOB1A binding, the presence of TmGpx1 is meaningful and motivates future experimental testing of whether TmGpx1 can modulate host Hippo-pathway-associated signaling during T. marneffei infection.