title: Poly(amidoamine)-based dendrimer/siRNA complexation studied by computer simulations: effects of pH and generation on dendrimer structure and siRNA binding.
abstract: In this work we report, compare and discuss the results obtained from fully atomistic molecular dynamics simulations of generations 4, 5, and 6 of PAMAM-based dendrimers having NH(3)  and triethanolamine as cores, forming complexes with a short interfering RNA (siRNA) at different pH values and at physiological ionic strength. By employing a detailed analysis we demonstrate how features such as molecular size, structural details, and protonation level of this category of dendrimers affect the dendrimer/siRNA complexation. Properties like the conformational flexibility of the dendrimer, the effective charge distribution of the assembly, and the level of intra- and intermolecular hydrogen bonding between the two molecular entities are all found to play a significant role in the mutual interactions between the nucleic acid and the hyperbranched molecules. All these features are of key importance in the multifaceted mechanism of dendrimer/gene complexation, and their understanding can provide valuable insight toward the design of more efficient nucleic acid nanocarriers.
authors.affiliation: Chemical Engineering Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. karatas@eng.auth.gr
authors.forename: Kostas
authors.initials: K
authors.lastname: Karatasos
authors.forename: Paola
authors.initials: P
authors.lastname: Posocco
authors.forename: Erik
authors.initials: E
authors.lastname: Laurini
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pricl
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D003198:Computer Simulation; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D004983:Ethanolamines / Q000737:chemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry*; D009994:Osmolar Concentration; D011073:Polyamines / Q000737:chemistry; D011522:Protons; D034741:RNA, Small Interfering / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D001672:Biocompatible Materials; D050091:Dendrimers; D004337:Drug Carriers; D004983:Ethanolamines; C104700:PAMAM Starburst; D011073:Polyamines; D011522:Protons; D034741:RNA, Small Interfering; C009546:triethanolamine