TY - JOUR
T1 - Poly(amidoamine) dendrimers on lipid bilayers I
T2 - Free energy and conformation of binding
AU - Kelly, Christopher V.
AU - Leroueil, Pascale R.
AU - Nett, Elizabeth K.
AU - Wereszczynski, Jeffery M.
AU - Baker, James R.
AU - Orr, Bradford G.
AU - Holl, Mark M.Banaszak
AU - Andricioaei, Ioan
PY - 2008/8/7
Y1 - 2008/8/7
N2 - Third-generation (G3) poly(amidoamine) (PAMAM) dendrimers are simulated approaching 1,2-dimyristoylsn-glycero-3-phosphocholine (DMPC) bilayers with fully atomistic molecular dynamics, which enables the calculation of a free energy profile along the approach coordinate. Three different dendrimer terminations are examined: protonated primary amine, uncharged acetamide, and deprotonated carboxylic acid. As the dendrimer and lipids become closer, their attractive force increases (up to 240 pN) and the dendrimer becomes deformed as it interacts with the lipids. The total energy release upon binding of a G3-NH3 +, G3-Ac, or G3-COO- dendrimer to a DMPC bilayer is, respectively, 36, 26, or 47 kcal/mol or, equivalently, 5.2, 3.2, or 4.7 × 10-3 kcal/g. These results are analyzed in terms of the dendrimers' size, shape, and atomic distributions as well as proximity of individual lipid molecules and particular lipid atoms to the dendrimer. For example, an area of 9.6, 8.2, or 7.9 nm2 is covered on the bilayer for the G3-NH3 +, G3-Ac, or G3-COO- dendrimers, respectively, while interacting strongly with 18-13 individual lipid molecules.
AB - Third-generation (G3) poly(amidoamine) (PAMAM) dendrimers are simulated approaching 1,2-dimyristoylsn-glycero-3-phosphocholine (DMPC) bilayers with fully atomistic molecular dynamics, which enables the calculation of a free energy profile along the approach coordinate. Three different dendrimer terminations are examined: protonated primary amine, uncharged acetamide, and deprotonated carboxylic acid. As the dendrimer and lipids become closer, their attractive force increases (up to 240 pN) and the dendrimer becomes deformed as it interacts with the lipids. The total energy release upon binding of a G3-NH3 +, G3-Ac, or G3-COO- dendrimer to a DMPC bilayer is, respectively, 36, 26, or 47 kcal/mol or, equivalently, 5.2, 3.2, or 4.7 × 10-3 kcal/g. These results are analyzed in terms of the dendrimers' size, shape, and atomic distributions as well as proximity of individual lipid molecules and particular lipid atoms to the dendrimer. For example, an area of 9.6, 8.2, or 7.9 nm2 is covered on the bilayer for the G3-NH3 +, G3-Ac, or G3-COO- dendrimers, respectively, while interacting strongly with 18-13 individual lipid molecules.
UR - http://www.scopus.com/inward/record.url?scp=49649089223&partnerID=8YFLogxK
U2 - 10.1021/jp801377a
DO - 10.1021/jp801377a
M3 - Article
AN - SCOPUS:49649089223
SN - 1520-6106
VL - 112
SP - 9337
EP - 9345
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 31
ER -