Atomic-Scale Molecular Dynamics Simulations of DNA-Polycation Complexes: Two Distinct Binding Patterns.
Synthetic cationic polymers represent a promising class of delivery vectors for gene therapy. Here, we employ atomistic molecular dynamics simulations to gain insight into the structure and properties of complexes of DNA with four linear polycations: polyethylenimine (PEI), poly-l-lysine (PLL), polyvinylamine (PVA), and polyallylamine (PAA). These polycations differ in their polymer geometries, protonation states, and hydrophobicities of their backbone chains. Overall, our results demonstrate for the first time the existence of two distinct patterns of binding of DNA with polycations. For PEI, PLL, and PAA, the complex is stabilized by the electrostatic attraction between protonated amine groups of the polycation and phosphate groups of DNA. In contrast, PVA demonstrates an alternative binding pattern as it gets embedded into the DNA major groove. It is likely that both the polymer topology and affinity of the backbone chain of PVA to the DNA groove are responsible for such behavior. The differences in binding patterns can have important biomedical implications: embedding PVA into a DNA groove makes it less sensitive to changes in the aqueous environment (pH level, ionic strength, etc.) and could therefore hinder the intracellular release of genetic material from a delivery vector, leading to lower transfection activity.
Faculty of Physics, St. Petersburg State University , Ulyanovskaya str. 3, Petrodvorets, St. Petersburg 198504, Russia.
Diana A
DA
Kondinskaia
Faculty of Physics, St. Petersburg State University , Ulyanovskaya str. 3, Petrodvorets, St. Petersburg 198504, Russia.
Andrei Yu
AY
Kostritskii
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University , Leninskie Gory, 1/40, Moscow 119991, Russia.
Alexey M
AM
Nesterenko
Faculty of Physics, St. Petersburg State University , Ulyanovskaya str. 3, Petrodvorets, St. Petersburg 198504, Russia.
Alexandra Yu
AY
Antipina
Faculty of Physics, St. Petersburg State University , Ulyanovskaya str. 3, Petrodvorets, St. Petersburg 198504, Russia.|Institute of Macromolecular Compounds, Russian Academy of Sciences , Bolshoi Prospect V.O. 31, St. Petersburg 199004, Russia.
Andrey A
AA
Gurtovenko
D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D056004:Molecular Dynamics Simulation; D009994:Osmolar Concentration; D011073:Polyamines / Q000737:chemistry* / Q000378:metabolism; D000071228:Polyelectrolytes; D011107:Polylysine / Q000737:chemistry / Q000378:metabolism; D011145:Polyvinyls / Q000737:chemistry / Q000378:metabolism; D011522:Protons; D014867:Water / Q000737:chemistry
D004247:DNA; D011073:Polyamines; D000071228:Polyelectrolytes; D011107:Polylysine; D011145:Polyvinyls; D011522:Protons; D014867:Water; C534904:polyvinylamine; C063994:polyallylamine