All-atom constant pH MD (GROMACS lambda-dynamics CpHMD) of a self-assembled empty lipid nanoparticle without siRNA (DSPC:CHOL:MC3:DPG-PEG = 10:38.5:50:1.5) with titratable MC3 lipids, at pH 7, two replicas. Related to Figs. S13 & S14 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom constant pH MD (GROMACS lambda-dynamics CpHMD) of a self-assembled empty lipid nanoparticle without siRNA (DSPC:CHOL:MC3:DPG-PEG = 10:38.5:50:1.5) with titratable MC3 lipids, at pH 6, two replicas. Related to Figs. S13 & S14 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom constant pH MD (GROMACS lambda-dynamics CpHMD) of a self-assembled empty lipid nanoparticle without siRNA (DSPC:CHOL:MC3:DPG-PEG = 10:38.5:50:1.5) with titratable MC3 lipids, at pH 5, two replicas. Related to Figs. S13 & S14 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom constant pH MD (GROMACS lambda-dynamics CpHMD) of a self-assembled empty lipid nanoparticle without siRNA (DSPC:CHOL:MC3:DPG-PEG = 10:38.5:50:1.5) with titratable MC3 lipids, at pH 4, two replicas. Related to Figs. S13 & S14 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom constant pH MD (GROMACS lambda-dynamics CpHMD) of a self-assembled empty lipid nanoparticle without siRNA (DSPC:CHOL:MC3:DPG-PEG = 10:38.5:50:1.5) with titratable MC3 lipids, at pH 14, two replicas. Related to Figs. S13 & S14 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom constant pH MD (GROMACS lambda-dynamics CpHMD) of a self-assembled empty lipid nanoparticle without siRNA (DSPC:CHOL:MC3:DPG-PEG = 10:38.5:50:1.5) with titratable MC3 lipids, at pH 13, two replicas. Related to Figs. S13 & S14 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom constant pH MD (GROMACS lambda-dynamics CpHMD) of a self-assembled empty lipid nanoparticle without siRNA (DSPC:CHOL:MC3:DPG-PEG = 10:38.5:50:1.5) with titratable MC3 lipids, at pH 12, two replicas. Related to Figs. S13 & S14 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom constant pH MD (GROMACS lambda-dynamics CpHMD) of a self-assembled empty lipid nanoparticle without siRNA (DSPC:CHOL:MC3:DPG-PEG = 10:38.5:50:1.5) with titratable MC3 lipids, at pH 11, two replicas. Related to Figs. S13 & S14 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom constant pH MD (GROMACS lambda-dynamics CpHMD) of a self-assembled empty lipid nanoparticle without siRNA (DSPC:CHOL:MC3:DPG-PEG = 10:38.5:50:1.5) with titratable MC3 lipids, at pH 10, two replicas. Related to Figs. S13 & S14 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom (CHARMM36) system of a HER2-siRNA lipid nanoparticle fused through a stalk with an endosomal-like membrane in water with 100 mM KCl, with all ionizable MC3 lipids protonated and the siRNA reoriented. Unbiased MD studying siRNA translocation (Figure 4 and Fig. S17 of the paper). Trajectory without solvent.

All-atom (CHARMM36) system of a HER2-siRNA lipid nanoparticle fused through a stalk with an endosomal-like membrane (MC3, DSPC, cholesterol, PC/PE/PI/SM lipids) in water with 100 mM KCl, in which all ionizable MC3 lipids are neutral (deprotonated). Unbiased MD showing spontaneous siRNA translocation/release (Figure 4 and Fig. S17 of the paper). Trajectory without solvent.

All-atom (CHARMM36) system of a HER2-siRNA lipid nanoparticle fused through a stalk with an endosomal-like membrane (MC3, DSPC, cholesterol, PC/PE/PI/SM lipids) in water with 100 mM KCl, in which half of the ionizable MC3 lipids are neutral (148 protonated MC3H, 150 neutral MC3). Unbiased MD to study siRNA translocation/release (Figure 4 and Fig. S17 of the paper). Trajectory without solvent.

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 9.7) 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.

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.

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 8.7) 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.

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 8.2) 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.

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 7.7) 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.

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 7.6) 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.