Complexation of single stranded RNA with an ionizable lipid: an all-atom molecular dynamics simulation study
Complexation of a lipid-based ionizable cationic molecule (referred to as DML: see main text) with RNA in an aqueous medium was examined in detail by means of fully atomistic molecular dynamics simulations. The different stages of the DMLRNA association process were explored, while the structural ch...
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Published in | Soft matter Vol. 16; no. 3; pp. 6993 - 75 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Cambridge
Royal Society of Chemistry
14.08.2020
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Subjects | |
Online Access | Get full text |
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Summary: | Complexation of a lipid-based ionizable cationic molecule (referred to as DML: see main text) with RNA in an aqueous medium was examined in detail by means of fully atomistic molecular dynamics simulations. The different stages of the DMLRNA association process were explored, while the structural characteristics of the final complex were described. The self-assembly process of the DML molecules was examined in the absence and in the presence of nucleotide sequences of different lengths. The formed DML clusters were described in detail in terms of their size and composition and were found to share common features in all the examined systems. Different timescales related to their self-assembly and their association with RNA were identified. It was found that beyond a time period of a few tens of ns, a conformationally stable DMLRNA complex was formed, characterized by DML clusters covering the entire contour of RNA. In a system with a 642-nucleotide sequence, the average size of the complex in the longest dimension was found to be close to 40 nm. The DML clusters were characterized by a rather low surface charge, while a propensity for the formation of larger size clusters close to RNA was noted. Apart from hydrophobic and electrostatic interactions, hydrogen bonding was found to play a key-role in the DMLDML and in the DMLRNA association. The information obtained regarding the structural features of the final complex, the timescales and the driving forces associated with the complexation and the self-assembly processes provide new insight towards a rational design of optimized lipid-based ionizable cationic gene delivery vectors.
Complexation of a lipid-based ionizable cationic molecule with RNA in an aqueous medium was examined in detail by means of fully atomistic molecular dynamics simulations. |
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Bibliography: | 10.1039/d0sm00736f Electronic supplementary information (ESI) available. See DOI ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1744-683X 1744-6848 |
DOI: | 10.1039/d0sm00736f |