All-atom umbrella sampling window (reference RNA-LNP distance 0.7 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 0.2 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 9.9 nm) of siRNA translocation from an MC3-containing lipid nanoparticle (LNP) to the endosomal membrane after stalk formation, with fixed MC3 protonation states. Starting structures were taken from a steered MD pull along the distance (Y component) between the centres of mass of the LNP lipids near the RNA and the RNA phosphates. Data for Figures 4A and 4C (and Fig. S17) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (reference RNA-LNP distance 9.4 nm) of siRNA translocation from an MC3-containing lipid nanoparticle (LNP) to the endosomal membrane after stalk formation, with fixed MC3 protonation states. Starting structures were taken from a steered MD pull along the distance (Y component) between the centres of mass of the LNP lipids near the RNA and the RNA phosphates. Data for Figures 4A and 4C (and Fig. S17) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (reference RNA-LNP distance 8.9 nm) of siRNA translocation from an MC3-containing lipid nanoparticle (LNP) to the endosomal membrane after stalk formation, with fixed MC3 protonation states. Starting structures were taken from a steered MD pull along the distance (Y component) between the centres of mass of the LNP lipids near the RNA and the RNA phosphates. Data for Figures 4A and 4C (and Fig. S17) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (reference RNA-LNP distance 8.4 nm) of siRNA translocation from an MC3-containing lipid nanoparticle (LNP) to the endosomal membrane after stalk formation, with fixed MC3 protonation states. Starting structures were taken from a steered MD pull along the distance (Y component) between the centres of mass of the LNP lipids near the RNA and the RNA phosphates. Data for Figures 4A and 4C (and Fig. S17) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (reference RNA-LNP distance 7.9 nm) of siRNA translocation from an MC3-containing lipid nanoparticle (LNP) to the endosomal membrane after stalk formation, with fixed MC3 protonation states. Starting structures were taken from a steered MD pull along the distance (Y component) between the centres of mass of the LNP lipids near the RNA and the RNA phosphates. Data for Figures 4A and 4C (and Fig. S17) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (reference RNA-LNP distance 7.4 nm) of siRNA translocation from an MC3-containing lipid nanoparticle (LNP) to the endosomal membrane after stalk formation, with fixed MC3 protonation states. Starting structures were taken from a steered MD pull along the distance (Y component) between the centres of mass of the LNP lipids near the RNA and the RNA phosphates. Data for Figures 4A and 4C (and Fig. S17) of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery'.

All-atom umbrella sampling window (labelled 6.9) for the free energy of HER2 siRNA translocation from the LNP through the LNP-endosomal membrane stalk. The reaction coordinate is the Y distance between the LNP lipids near the RNA and the RNA phosphates. Data related to the manuscript 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. 4).

All-atom umbrella sampling window (labelled 6.4) for the free energy of HER2 siRNA translocation from the LNP through the LNP-endosomal membrane stalk. The reaction coordinate is the Y distance between the LNP lipids near the RNA and the RNA phosphates. Data related to the manuscript 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. 4).

All-atom umbrella sampling window (labelled 5.4) for the free energy of HER2 siRNA translocation from the LNP through the LNP-endosomal membrane stalk. The reaction coordinate is the Y distance between the LNP lipids near the RNA and the RNA phosphates. Data related to the manuscript 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. 4).

All-atom umbrella sampling window (labelled 3.9) for the free energy of HER2 siRNA translocation from the LNP through the LNP-endosomal membrane stalk. The reaction coordinate is the Y distance between the LNP lipids near the RNA and the RNA phosphates. Data related to the manuscript 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. 4).

All-atom umbrella sampling window (labelled 3.4) for the free energy of HER2 siRNA translocation from the LNP through the LNP-endosomal membrane stalk. The reaction coordinate is the Y distance between the LNP lipids near the RNA and the RNA phosphates. Data related to the manuscript 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. 4).

All-atom umbrella sampling window (labelled 2.9) for the free energy of HER2 siRNA translocation from the LNP through the LNP-endosomal membrane stalk. The reaction coordinate is the Y distance between the LNP lipids near the RNA and the RNA phosphates. Data related to the manuscript 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. 4).

All-atom umbrella sampling window (labelled 2.4) for the free energy of HER2 siRNA translocation from the LNP through the LNP-endosomal membrane stalk. The reaction coordinate is the Y distance between the LNP lipids near the RNA and the RNA phosphates. Data related to the manuscript 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. 4).

All-atom umbrella sampling window (labelled 10.9) for the free energy of HER2 siRNA translocation from the LNP through the LNP-endosomal membrane stalk. The reaction coordinate is the Y distance between the LNP lipids near the RNA and the RNA phosphates. Data related to the manuscript 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. 4).

All-atom umbrella sampling window (labelled 10.4) for the free energy of HER2 siRNA translocation from the LNP through the LNP-endosomal membrane stalk. The reaction coordinate is the Y distance between the LNP lipids near the RNA and the RNA phosphates. Data related to the manuscript 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. 4).

All-atom umbrella sampling window (labelled 1.9) for the free energy of HER2 siRNA translocation from the LNP through the LNP-endosomal membrane stalk. The reaction coordinate is the Y distance between the LNP lipids near the RNA and the RNA phosphates. Data related to the manuscript 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. 4).