Complexation of single stranded RNA with an ionizable lipid: an all-atom molecular dynamics simulation study
Anastassia N Rissanou1, Andreas Ouranidis, Kostas Karatasos
1Department of Chemical Engineering, University of Thessaloniki, P.O. BOX 420, 54124 Thessaloniki, Greece. risanou@uoc.gr karatas@eng.auth.gr.
Soft Matter
|July 16, 2020
Summary
Molecular dynamics simulations reveal how lipid-based ionizable cationic molecules self-assemble and complex with RNA. Stable complexes form, with molecules covering RNA and driven by various interactions, aiding gene delivery vector design.
Area of Science:
- Biochemistry
- Materials Science
- Computational Chemistry
Background:
- Lipid-based ionizable cationic molecules are promising for gene delivery.
- Understanding their complexation with RNA is crucial for optimizing vector design.
Purpose of the Study:
- To investigate the complexation of a specific lipid-based ionizable cationic molecule (DML) with RNA.
- To explore the self-assembly process of DML molecules and their structural characteristics within the complex.
Main Methods:
- Fully atomistic molecular dynamics simulations were employed.
- The association process, self-assembly, and structural features of DML-RNA complexes were analyzed.
Main Results:
- Stable DML-RNA complexes form within tens of nanoseconds, with DML clusters covering the RNA.
- DML self-assembly and RNA association are influenced by molecule size and driven by hydrophobic, electrostatic, and hydrogen bonding interactions.
- A 642-nucleotide RNA complex reached approximately 40 nm in size, with DML clusters showing low surface charge and a propensity for larger sizes near RNA.
Conclusions:
- The study provides detailed insights into the structural features, timescales, and driving forces of DML-RNA complexation and self-assembly.
- Findings contribute to the rational design of advanced lipid-based ionizable cationic gene delivery vectors.
