Multiscale modeling of the cellular uptake of C6 peptide-siRNA complexes

In this study, multiscaled computational simulations of these peptides were performed in aqueous media, interrogating the relationship between the structure and behaviour. All atom molecular dynamic (MD) simulation results show that all CPPs show stable α-helical amphipathic secondary structures. Furthermore, docking calculations indicate that the C6 peptides can fit into the major groove of the siRNA double-helix, and once filled, could bind randomly along the minor grooves and to other, previously bound peptides. Coarse grained MD simulations were also used to generate free energy profiles for the dimerization of peptides, and binding of the peptide to siRNA. Simulation results confirm that all peptides favour binding to siRNA, they however, also favour dimerization. This affinity for aggregation may trigger the formation of larger complexes with siRNA and enhance the cellular uptake. These results indicate the capacity of C6 peptides as efficient delivery vehicles. As expected the amino acid sequence plays a crucial role in the helicity, peptide self-assembly, interaction of peptide with cell membrane and formation of stable siRNA-CPP complex.PMID:35462199 | DOI:10.1016/j.compbiolchem.2022.107679

Source: Computational Biology and Chemistry - April 24, 2022 Category: Bioinformatics Authors: P W C M Purijjala P V G M Rathnayake B T Kumara B C M Gunathunge R A A P Ranasinghe D N Karunaratne R J K U Ranatunga Source Type: research