LNP-endosome siRNA translocation: umbrella sampling with constant-pH MD, window 1.7 nm

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'.