Free energy profiles of lipid flip-flop in a proteinless POPC membrane (black) and along the MTCH2 scrambling pathway (red, blue, and purple). In both models, the presence of MTCH2 dramatically reduces the flip-flop free energy barrier. The red arrow in the Martini 2 chart indicates a peak in the free energy profile corresponding to the hydrophobic gate. The calculation error is <1 kJ mol-1. SeeFigure S3for detailed view of free energy calculations convergence.
