Impact of salt on AAV8 capsid aggregation with single-stranded DNA: insights from coarse-grained molecular dynamics...

This study employed coarse-grained molecular dynamics (CG-MD) simulations to explore the aggregation dynamics of adeno-associated viral (AAV) capsids under various ionic conditions, with a particular focus on the effects of sodium chloride (NaCl) and magnesium chloride (MgCl₂). Our simulations revealed that AAV8 capsid aggregation was observed at lower concentrations of NaCl (0.05 M) possibly due to insufficient charge screening. In contrast, higher concentrations of NaCl were found to minimize capsid aggregation, likely due to enhanced charge screening that could limit the interactions responsible for aggregation. Magnesium ions (Mg²⁺) stabilized the capsid structure by primarily acting as counter ions binding to the negatively charged DNA, effectively compacting the DNA inside the capsid. This compaction likely altered the spatial arrangement of charges on the capsid surface, leading to a reduced tendency for aggregation. This detailed understanding of how different salt concentrations and types affect viral capsid behavior is crucial for overall understanding of their stability and underscores the potential use of CG-MD simulations as a methodology for studying these systems.