Molecular Fingerprint of Cold Adaptation in Antarctic Icefish PepT1 (<i>Chionodraco hamatus</i>): A Comparative Molecular Dynamics Study.

ABSTRACT: Cold environments challenge the structural and functional integrity of membrane proteins, requiring specialized adaptations to maintain activity under low thermal energy. Here, we investigate the molecular basis of cold tolerance in the peptide transporter PepT1 from the Antarctic icefish (Chionodraco hamatus, ChPepT1) using molecular dynamics simulations, binding free energy calculations (MM/GBSA), and dynamic network analysis. We compare ChPepT1 to its human ortholog (hPepT1), a non-cold-adapted variant, to reveal key features enabling psychrophilic function. Our simulations show that ChPepT1 displays enhanced global flexibility, particularly in domains adjacent to the substrate-binding site and the C-terminal domain (CTD). While hPepT1 loses substrate binding affinity as temperat

SUBMITTER: Carrasco-Faus G 

PROVIDER: S-EPMC12383401 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature