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 6.8) 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 6.7) 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 6.2) 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 5.7) 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 5.6) 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.

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 5.2) 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 4.7) 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 4.2) 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 4.1) 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 3.7) 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 umbrella sampling window (reference RNA-LNP distance 3.5 nm) combined with constant-pH MD (lambda dynamics, pH 6.5, all MC3 ionizable lipids titratable with buffer particles) for siRNA translocation from an MC3-containing lipid nanoparticle to the endosomal membrane after stalk formation. The collective variable is the Y-component distance between the centres of mass of LNP lipids near the RNA and the RNA phosphates. Data for Figure 4B (and Fig. S18) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (reference RNA-LNP distance 3.2 nm) combined with constant-pH MD (lambda dynamics, pH 6.5, all MC3 ionizable lipids titratable with buffer particles) for siRNA translocation from an MC3-containing lipid nanoparticle to the endosomal membrane after stalk formation. The collective variable is the Y-component distance between the centres of mass of LNP lipids near the RNA and the RNA phosphates. Data for Figure 4B (and Fig. S18) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (reference RNA-LNP distance 2.7 nm) combined with constant-pH MD (lambda dynamics, pH 6.5, all MC3 ionizable lipids titratable with buffer particles) for siRNA translocation from an MC3-containing lipid nanoparticle to the endosomal membrane after stalk formation. The collective variable is the Y-component distance between the centres of mass of LNP lipids near the RNA and the RNA phosphates. Data for Figure 4B (and Fig. S18) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (reference RNA-LNP distance 11.2 nm) combined with constant-pH MD (lambda dynamics, pH 6.5, all MC3 ionizable lipids titratable with buffer particles) for siRNA translocation from an MC3-containing lipid nanoparticle to the endosomal membrane after stalk formation. The collective variable is the Y-component distance between the centres of mass of LNP lipids near the RNA and the RNA phosphates. Data for Figure 4B (and Fig. S18) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (reference RNA-LNP distance 10.7 nm) combined with constant-pH MD (lambda dynamics, pH 6.5, all MC3 ionizable lipids titratable with buffer particles) for siRNA translocation from an MC3-containing lipid nanoparticle to the endosomal membrane after stalk formation. The collective variable is the Y-component distance between the centres of mass of LNP lipids near the RNA and the RNA phosphates. Data for Figure 4B (and Fig. S18) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (reference RNA-LNP distance 10.2 nm) combined with constant-pH MD (lambda dynamics, pH 6.5, all MC3 ionizable lipids titratable with buffer particles) for siRNA translocation from an MC3-containing lipid nanoparticle to the endosomal membrane after stalk formation. The collective variable is the Y-component distance between the centres of mass of LNP lipids near the RNA and the RNA phosphates. Data for Figure 4B (and Fig. S18) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (reference RNA-LNP distance 1.8 nm) combined with constant-pH MD (lambda dynamics, pH 6.5, all MC3 ionizable lipids titratable with buffer particles) for siRNA translocation from an MC3-containing lipid nanoparticle to the endosomal membrane after stalk formation. The collective variable is the Y-component distance between the centres of mass of LNP lipids near the RNA and the RNA phosphates. Data for Figure 4B (and Fig. S18) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (reference RNA-LNP distance 1.7 nm) combined with constant-pH MD (lambda dynamics, pH 6.5, all MC3 ionizable lipids titratable with buffer particles) for siRNA translocation from an MC3-containing lipid nanoparticle to the endosomal membrane after stalk formation. The collective variable is the Y-component distance between the centres of mass of LNP lipids near the RNA and the RNA phosphates. Data for Figure 4B (and Fig. S18) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (reference RNA-LNP distance 1.3 nm) combined with constant-pH MD (lambda dynamics, pH 6.5, all MC3 ionizable lipids titratable with buffer particles) for siRNA translocation from an MC3-containing lipid nanoparticle to the endosomal membrane after stalk formation. The collective variable is the Y-component distance between the centres of mass of LNP lipids near the RNA and the RNA phosphates. Data for Figure 4B (and Fig. S18) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.