@article{ISI:000282478500053,
 abstract = {This paper reports the structural behavior and thermodynamics of the
complexation of siRNA with poly(amidoamine) (PAMAM) dendrimers of
generation 3 (G3) and 4 (G4) through fully atomistic molecular dynamics
(MD) simulations accompanied by free energy calculations and inherent
structure determination. We have also done simulation with one siRNA and
two dendrimers (2 x G3 or 2xG4) to get the microscopic picture of
various binding modes. Our simulation results reveal the formation of
stable siRNA-dendrimer complex over nanosecond time scale. With the
increase in dendrimcr generation, the charge ratio increases and hence
the binding energy between siRNA and dendrimer also increases in
accordance with available experimental measurements. Calculated radial
distribution functions of amines groups of various subgenerations in a
given generation of dendrimer and phosphate in backbone of siRNA reveals
that one dendrimer of generation 4 shows better binding with siRNA
almost wrapping the dendrimer when compared to the binding with lower
generation dendrimer like G3. In contrast, two dendrimers of generation
4 show binding without siRNA wrapping the den-rimer because of repulsion
between two dendrimers. The counterion distribution around the complex
and the water molecules in the hydration shell of siRNA give microscopic
picture of the binding dynamics. We see a clear correlation between
water. counterions motions and the complexation i.e. the water molecules
and counterions which condensed around siRNA are moved away from the
siRNA backbone when dendrimer start binding to the siRNA back hone. As
siRNA wraps/bind to the dendrimer counterions originally condensed onto
siRNA (Na-1) and dendrimer (Cl-) get released. We give a quantitative
estimate of the entropy of counterions and show that there is gain in
entropy due to counterions release during the complexation. Furthermore,
the free energy of complexation of IG3 and IG4 at two different salt
concentrations shows that increase in salt concentration leads to the
weakening of the binding affinity of siRNA and dendrimer.},
 author = {Vasumathi, V. and Maiti, Prabal K.},
 doi = {10.1021/ma1012495},
 eissn = {1520-5835},
 issn = {0024-9297},
 journal = {MACROMOLECULES},
 month = {OCT 12},
 number = {19},
 orcid-numbers = {V, Vasumathi/0000-0002-0115-1615
Maiti, Prabal/0000-0002-9956-1136
velachi, vasumathi/0000-0002-0115-1615},
 pages = {8264-8274},
 researcherid-numbers = {V, Vasumathi/D-4775-2013
Maiti, Prabal/B-6335-2009
velachi, vasumathi/M-8476-2019},
 times-cited = {78},
 title = {Complexation of siRNA with Dendrimer: A Molecular Modeling Approach},
 unique-id = {ISI:000282478500053},
 volume = {43},
 year = {2010}
}