All-atom umbrella sampling window (labelled 5.9) 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 4.9) 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 4.4) 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 0.4) 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 constant pH MD (CpHMD, lambda dynamics) of the small self-assembled HER2-siRNA lipid nanoparticle backmapped from coarse-grained, at pH 14. All 300 MC3 lipids are titratable. Full system including water and ions. Two replicas. Related to Figure 2 and Figs. S8-S11 of the paper.

All-atom constant pH MD (CpHMD, lambda dynamics) of the small self-assembled HER2-siRNA lipid nanoparticle backmapped from coarse-grained, at pH 9. Full system including water and ions. Two replicas. Related to Figure 2 and Figs. S8-S11 of the paper.

All-atom constant pH MD (CpHMD, lambda dynamics) of the small self-assembled HER2-siRNA lipid nanoparticle backmapped from coarse-grained, at pH 8. Full system including water and ions. Two replicas. Related to Figure 2 and Figs. S8-S11 of the paper.

All-atom constant pH MD (CpHMD, lambda dynamics) of the small self-assembled HER2-siRNA lipid nanoparticle backmapped from coarse-grained, at pH 7. Full system including water and ions. Two replicas. Related to Figure 2 and Figs. S8-S11 of the paper.

All-atom constant pH MD (CpHMD, lambda dynamics) of the small self-assembled HER2-siRNA lipid nanoparticle backmapped from coarse-grained, at pH 6. Full system including water and ions. Two replicas. Related to Figure 2 and Figs. S8-S11 of the paper.

All-atom constant pH MD (CpHMD, lambda dynamics) of the small self-assembled HER2-siRNA lipid nanoparticle backmapped from coarse-grained, at pH 5. Full system including water and ions. Two replicas. Related to Figure 2 and Figs. S8-S11 of the paper.

All-atom constant pH MD (CpHMD, lambda dynamics) of the small self-assembled HER2-siRNA lipid nanoparticle backmapped from coarse-grained, at pH 4. Full system including water and ions. Two replicas. Related to Figure 2 and Figs. S8-S11 of the paper.

All-atom constant pH MD (CpHMD, lambda dynamics) of the small self-assembled HER2-siRNA lipid nanoparticle (MC3, DSPC, cholesterol, PEG-lipid DPG2) backmapped from coarse-grained, at pH 13. All 300 MC3 lipids are titratable. Full system including water, ions and buffer particles. Two replicas. Related to Figure 2 and Figs. S8-S11 of the paper.

All-atom constant pH MD (GROMACS CpHMD lambda dynamics) of the simplified self-assembled HER2-siRNA lipid nanoparticle (siRNA, 300 titratable MC3 ionizable lipids, DSPC, cholesterol, DMG-PEG) in explicit water and ions at pH 12. Two replicas.

All-atom constant pH MD (GROMACS CpHMD lambda dynamics) of the simplified self-assembled HER2-siRNA lipid nanoparticle (siRNA, 300 titratable MC3 ionizable lipids, DSPC, cholesterol, DMG-PEG) in explicit water and ions at pH 11. Two replicas.

All-atom constant pH MD (GROMACS CpHMD lambda dynamics) of the simplified self-assembled HER2-siRNA lipid nanoparticle (siRNA, 300 titratable MC3 ionizable lipids, DSPC, cholesterol, DMG-PEG) in explicit water and ions at pH 10. Two replicas.

All-atom steered MD in which the HER2 siRNA is pulled away from the LNP lipids, through the LNP-endosomal membrane stalk, to transfect it. The pull is an umbrella-type moving restraint along Y (rate 0.0003 nm/ps, k 1000 kJ/mol/nm^2). The frames were used to set up the umbrella sampling windows. Data related to the manuscript 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. 4).

All-atom simulation of a MC3-based lipid nanoparticle (LNP) carrying a HER2 siRNA, fused with a model endosomal membrane at the stalk stage. The system was backmapped from the coarse-grained stalk state with CG2AT, in water with 100 mM KCl. The trajectory is saved with a 20 ns stride and includes the solvent. Data related to the manuscript 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. 3).

All-atom MD of an empty lipid nanoparticle (no siRNA cargo): 300 protonated MC3, 228 cholesterol, 60 DSPC and 12 PEG-lipid DPG2 in water with KCl. It was backmapped from coarse-grained with CG2AT. Trajectories without solvent. Four replicas. Related to the study of empty LNPs (Figs. S12-S14).