(5be) Multiscale Simulations of Peptides, Nanoparticles, Polymers, and Membranes for Drug Delivery and Nanopore Applications

Interactions of peptides, nanoparticles, polymers, and
membranes have been studied using all-atom and coarse-grained molecular
dynamics simulations. The following topics will be presented: (1) structure of
peptides interacting with monolayers and micelles [1,2,3,4]; (2) membrane
curvature and pore formation induced by differently sized, charged, shaped, and
concentrated nanoparticle (dendrimer) and linear polymer [5,6,7,8,9]; (3)
conformation and hydrodynamics of polyethylene glycol (PEG) in water and on surfaces
[10,11]; (4) self-assembly and phase behavior of PEG-conjugated liposomes,
bicelles, and micelles [12,13]; (5) parameterization of all-atom and
coarse-grained models for simulations described above. This work aids in the
rational design of synthetic peptides, nanoparticles, and drug complexes for
drug delivery, and development of accurate nanopores for biosensor
applications. Future research directions are presented.

References

[1] Lee H, Kandasamy
SK, and Larson RG, Molecular dynamics simulations of the anchoring and tilting
of the lung-surfactant peptide SP-B_1-25 in palmitic acid monolayers.
Biophysical J., 2005,
89:3807-3821

[2] Sayer JA, Otto EA, O'toole JF, Nurnberg G, Kennedy MA,
Becker C, Hennies HC, Helou J, Attanasio M, Fausett BV, Utsch B, Khanna H, Liu
Y, Lee H, Larson RG, and Hildebrandt F
et al., The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome
and activates transcription factor ATF4. Nature Genetics, 2006, 38:674-681

[3] Lee H, and
Larson RG, Prediction of the stability of coiled coils using molecular dynamics
simulations. Molecular Simulation, 2007, 33:463-473

[4] Low C, Weininger U, Lee H, Schweimer K, Pastor RW, and Balbach J. Structure and dynamics of
Helix-0 of the N-BAR domain in lipid micelles and bilayers. Biophysical
J., 2008, 95:4315-4323

[5] Lee H, Baker JR,
and Larson RG, Molecular dynamics studies of the size, shape, and internal
structure of 0% and 90%-acetylated G5 PAMAM dendrimers in water and methanol. J.
Physical Chemistry B., 2006,
110:4014-4019

[6] Lee H, and
Larson RG, Molecular dynamics simulations of PAMAM dendrimer-induced pore
formation in DPPC bilayers using a coarse grained model. J.
Physical Chemistry B., 2006,
110:18204-18211

[7] Lee H, and
Larson RG. Coarse-grained molecular dynamics studies of the concentration and
size dependence of fifth- and seventh-generation PAMAM dendrimers on pore
formation in DMPC bilayer. J. Physical Chemistry B., 2008, 112:7778-7784

[8] Lee H, and
Larson RG, Lipid bilayer curvature and pore formation induced by charged linear
polymers and dendrimers: the effect of molecular shape. J.
Physical Chemistry B., 2008, 112:12279-12285

[9] Lee H, and
Larson RG, Multiscale modeling of dendrimers and their interactions with
bilayers and polyelectrolytes. Molecules, 2009, 14:423-438

[10] Lee H, Venable
RM, MacKerell AD, and Pastor RW. Molecular dynamics studies of polyethylene
oxide and polyethylene glycol: Hydrodynamic radius and shape anisotropy. Biophysical
J., 2008, 95:1590-1599

[11] Lee H, de Vries
AH, Marrink SJ, and Pastor RW, A coarse-grained model for polyethylene oxide
and polyethylene glycol: conformation and hydrodynamics. J.
Physical Chemistry B., 2009, 113:13186-13194

[12] Lee H, and
Larson RG, Molecular dynamics study of the structure and interparticle
interactions of polyethylene glycol-conjugated PAMAM dendrimers. J.
Physical Chemistry B., 2009, 113:13202-13207

[13] Lee H, and
Pastor RW, Polyethylene glycol concentration dependence of phase behaviors of
self-assembled vesicles, bicelles, and micelles. J. Am. Chem. Soc. In preparation.