All-atom constant pH MD (CpHMD, lambda dynamics) of the small self-assembled HER2-siRNA lipid nanoparticle backmapped from coarse-grained, at pH 5. All 300 MC3 lipids are titratable. Trajectories without solvent. 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. All 300 MC3 lipids are titratable. Trajectories without solvent. 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. Trajectories without solvent. 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, titratable MC3 ionizable lipids, DSPC, cholesterol, DMG-PEG) in explicit water at pH 12. Two replicas. Solvent-stripped trajectories with titrating MC3 lipids renamed according to their protonation state.

All-atom (CHARMM36) simulation of the small HER2-siRNA LNP in contact with an endosomal membrane vesicle after stalk formation (backmapped from Martini 3 with CG2AT), in which the siRNA was manually reoriented perpendicular to the membrane; the RNA relaxed back to a surface-aligned configuration. Part of the study of pH-driven mechanisms of LNP-mediated siRNA endosomal escape.

All-atom (CHARMM36) simulation of the small HER2-siRNA LNP in contact with an endosomal membrane vesicle after stalk formation, backmapped from Martini 3 with CG2AT, in which 50% of the protonated ionizable lipids (MC3H) were converted to neutral MC3. Part of the study of pH-driven mechanisms of LNP-mediated siRNA endosomal escape.

Calibration (parametrization) run for constant pH MD of the ionizable lipid DLin-MC3-DMA (MC3) following the phbuilder parameterization procedure: a single MC3 lipid with a neutralizing buffer particle in TIP3P water, lambda coordinate fixed at 1.10 (buffer -0.10), used to fit the dV/dlambda coefficients. Part of the data of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. S19).

Calibration (parametrization) run for constant pH MD of the ionizable lipid DLin-MC3-DMA (MC3) following the phbuilder parameterization procedure: a single MC3 lipid with a neutralizing buffer particle in TIP3P water, lambda coordinate fixed at 1.00 (buffer 0.00), used to fit the dV/dlambda coefficients. Part of the data of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. S19).

Calibration (parametrization) run for constant pH MD of the ionizable lipid DLin-MC3-DMA (MC3) following the phbuilder parameterization procedure: a single MC3 lipid with a neutralizing buffer particle in TIP3P water, lambda coordinate fixed at 0.90 (buffer 0.10), used to fit the dV/dlambda coefficients. Part of the data of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. S19).

Calibration (parametrization) run for constant pH MD of the ionizable lipid DLin-MC3-DMA (MC3) following the phbuilder parameterization procedure: a single MC3 lipid with a neutralizing buffer particle in TIP3P water, lambda coordinate fixed at 0.80 (buffer 0.20), used to fit the dV/dlambda coefficients. Part of the data of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. S19).

Calibration (parametrization) run for constant pH MD of the ionizable lipid DLin-MC3-DMA (MC3) following the phbuilder parameterization procedure: a single MC3 lipid with a neutralizing buffer particle in TIP3P water, lambda coordinate fixed at 0.70 (buffer 0.30), used to fit the dV/dlambda coefficients. Part of the data of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery' (Fig. S19).

Calibration run for the constant pH MD parametrization of the ionizable lipid DLin-MC3-DMA (MC3), following the phbuilder workflow: a single MC3 molecule in water with ions and a buffer particle, position-restrained, with lambda fixed at 0.60 (buffer 0.40), 1 ns, used to fit the dV/dlambda correction (Fig. S19 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery').

Calibration run for the constant pH MD parametrization of the ionizable lipid DLin-MC3-DMA (MC3), following the phbuilder workflow: a single MC3 molecule in water with ions and a buffer particle, position-restrained, with lambda fixed at 0.50 (buffer 0.50), 1 ns, used to fit the dV/dlambda correction (Fig. S19 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery').

Calibration run for the constant pH MD parametrization of the ionizable lipid DLin-MC3-DMA (MC3), following the phbuilder workflow: a single MC3 molecule in water with ions and a buffer particle, position-restrained, with lambda fixed at 0.40 (buffer 0.60), 1 ns, used to fit the dV/dlambda correction (Fig. S19 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery').

Calibration run for the constant pH MD parametrization of the ionizable lipid DLin-MC3-DMA (MC3), following the phbuilder workflow: a single MC3 molecule in water with ions and a buffer particle, position-restrained, with lambda fixed at 0.30 (buffer 0.70), 1 ns, used to fit the dV/dlambda correction (Fig. S19 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery').

Calibration run for the constant pH MD parametrization of the ionizable lipid DLin-MC3-DMA (MC3), following the phbuilder workflow: a single MC3 molecule in water with ions and a buffer particle, position-restrained, with lambda fixed at 0.20 (buffer 0.80), 1 ns, used to fit the dV/dlambda correction (Fig. S19 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery').

Calibration run for the constant pH MD parametrization of the ionizable lipid DLin-MC3-DMA (MC3), following the phbuilder workflow: a single MC3 molecule in water with ions and a buffer particle, position-restrained, with lambda fixed at 0.10 (buffer 0.90), 1 ns, used to fit the dV/dlambda correction (Fig. S19 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery').

Calibration run for the constant pH MD parametrization of the ionizable lipid DLin-MC3-DMA (MC3), following the phbuilder workflow: a single MC3 molecule in water with ions and a buffer particle, position-restrained, with lambda fixed at -0.10 (buffer 1.10), 1 ns, used to fit the dV/dlambda correction (Fig. S19 of 'When lipids embrace RNA: pH-driven dynamics and mechanisms of LNP-mediated siRNA delivery').