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.