Abstract
Recently,lipid nanoparticles(LNPs)have been extensively investigated as non-viral carriers of nucleic acid vaccines due to their high transport efficiency,safety,and straightforward production and scalability.However,the molecular mech-anism underlying the interactions between nucleic acids and phospholipid bilayers within LNPs remains elusive.In this study,we employed the all-atom molecular dynamics simulation to investigate the interactions between single-stranded nucleic acids and a phospholipid bilayer.Our findings revealed that hydrophilic bases,specifically G in single-stranded RNA(ssRNA)and single-stranded DNA(ssDNA),displayed a higher propensity to form hydrogen bonds with phospho-lipid head groups.Notably,ssRNA exhibited stronger binding energy than ssDNA.Furthermore,divalent ions,particularly Ca2+,facilitated the binding of ssRNA to phospholipids due to their higher binding energy and lower dissociation rate from phospholipids.Overall,our study provides valuable insights into the molecular mechanisms underlying nucleic acid-phospholipid interactions,with potential implications for the nucleic acids in biotherapies,particularly in the context of lipid carriers.
基金项目
National Natural Science Foundation of China(12222506)
National Natural Science Foundation of China(12347102)
National Natural Science Foundation of China(12174184)
NETL
NSTL
维普
万方数据