LNP-endosome siRNA translocation: umbrella sampling with constant-pH MD, window 9.2

All-atom (CHARMM36) system of a HER2-siRNA lipid nanoparticle (DLin-MC3-DMA, DSPC, cholesterol) fused with an endosomal-like membrane through a stalk, in water with 100 mM KCl. Umbrella sampling window (directory 9.2) along the LNP–RNA distance coordinate combined with constant-pH MD (lambda dynamics of the ionizable MC3 lipids at pH 6.5), to relate siRNA translocation to MC3 protonation (Figure 4B and Fig. S18 of the paper). Trajectory without solvent.

Program

GROMACS 2021