Data for: Energetics of substrate transport in proton-dependent oligopeptide transporters

The PepTSo transporter mediates the transport of peptides across
biological membranes. Despite advancements in structural biology,
including cryogenic electron microscopy structures resolving PepTSo in
different states, the molecular basis of peptide recognition and transport
by PepTSo is not fully elucidated. In this study, we used molecular
dynamics simulations, Markov State Models (MSMs), and Transition Path
Theory (TPT) to investigate the transport mechanism of an alanine-alanine
peptide (Ala-Ala) through the PepTSo transporter. Our simulations revealed
conformational changes and key intermediate states involved in peptide
translocation. We observed that the presence of the Ala-Ala peptide
substrate lowers the free energy barriers associated with transition to
the inward-facing state. We also show a proton transport model and
analyzed the pharmacophore features of intermediate states, providing
insights for rational drug design. These findings highlight the
significance of substrate binding in modulating the conformational
dynamics of PepTSo and identify critical residues that facilitate
transport.