(584av) Mesoscopic Simulation of DNA - PAMAM Dendrimer Interactions | AIChE

(584av) Mesoscopic Simulation of DNA - PAMAM Dendrimer Interactions


Yu, S. - Presenter, University of Minnesota Twin Cities
Larson, R., University of Michigan

Poly(amido amine) dendrimers (PAMAM dendrimer), which are able to condense semiflexible dsDNA, allowing it to penetrate cell membranes, has many applications in gene therapy and drug delivery. Due to the similarity of the highly charged surface of PAMAM dendrimers and that of histones, the DNA-dendrimer complex mimics  chromatin. Since atomistic molecular dynamics simulations of chromatin formation, which is of great interest, is extremely expensive, we developed a coarse-grained model of PAMAM dendrimer-DNA interactions that tracks the dsDNA wrapping around a dendrimer. To speed up our Monte-Carlo simulations of dendrimer-DNA complex formation, we used an implicit solvent model and resolved the DNA double helix structure using the force field developed by de Pablo and coworkers. [PUT IN REF] By using this coarse-grained model, we are able to investigate large systems, without sacrificing important properties of DNA, such as sequence-dependent melting and bending. To eliminate the inherent cytotoxicity of dendrimer, the surface positive charges of PAMAM dendrimer can be partially neutralized by acetylation or PEGylation, which may also reduce its capability to condense DNA. Therefore, we used our simulations to explore the effects of PAMAM dendrimer surface charge density on DNA condensation, in order to help find the optimal charge density of the PAMAM dendrimer.