TY - JOUR

T1 - Atomic-Scale Molecular Dynamics Simulations of DNA-Polycation Complexes: Two Distinct Binding Patterns

AU - Kondinskaia, D.A.

AU - Kostritskii, A.Y.

AU - Nesterenko, A.M.

AU - Antipina, A.Y.

AU - Gurtovenko, A.A.

PY - 2016

Y1 - 2016

N2 - 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 bindin

AB - 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 bindin

U2 - 10.1021/acs.jpcb.6b03779

DO - 10.1021/acs.jpcb.6b03779

M3 - Article

VL - 120

SP - 6546

EP - 6554

JO - Journal of Physical Chemistry B

JF - Journal of Physical Chemistry B

SN - 1520-6106

IS - 27

ER -