抄録
This study focuses on analyzing the function of membrane transport proteins using high-precision all-atom molecular dynamics (MD) simulations, examining three key proteins: the sodium/proton antiporter A (NhaA), the light-driven proton pump bacteriorhodopsin, and the multidrug and toxic compound extrusion (MATE) transporter. For NhaA, it was found that the membrane of the cyclopropane fatty acid synthase gene disruptant showed tighter lipid packing and stronger interactions with NhaA compared to wild-type membranes, resulting in significant conformational changes in transmembrane helix 5 and enhanced Na transport activity. In the study of bacteriorhodopsin, new lipid force fields for archaeal membranes were developed, revealing that light activation strengthens interactions between retinal and key amino acids (Asp212 and Asp85) and highlighting the role of water molecule dynamics in proton transport. Differences in interactions between bacteriorhodopsin and archaeal membranes versus phosphatidylethanolamine (PE) membranes were also explored, showing significant structural impacts due to lipid composition. In the study of the MATE transporter, systems with varying protonation states of conserved acidic residues (Asp36, Glu255, Asp371) were examined, revealing that these residues play crucial roles in ion binding and transport. In particular, it was suggested that the protonation of Asp371 facilitates sodium uptake in the outward-facing state and supports sodium trapping by Glu255 in the inward-facing state. These findings provide detailed insights into the dynamic behavior and interaction mechanisms of membrane transport proteins, highlighting the importance of lipid composition and conserved residues in their function, contributing to a deeper understanding of membrane protein behavior, and informing drug development, biotechnological applications, and microbial-based production.
