MULTISCALE MOLECULAR MODELING AND RATIONAL DESIGN OF POLYMER BASED GENE DELIVERY VECTORS
We used multiscale modeling techniques and investigated several issues in non-viral based gene delivery using polyethyelenimine (PEI). Atomistic molecular dynamic simulations captured the spontaneous complex formation between a short PEI chain or a poly(L-lysine) (PLL) chain with DNA helices. Atomic structures obtained for DNA/PEI and DNA/PLL complexes compared very well with X-ray diffraction data. A computational Monte Carlo titration model was developed and was used to investigate the protonation state of PEI. The PEI was found to have about 55％ of amine groups protonated at physiological condition, thereby supporting the potential hypothesis of the proton sponge effect of PEI. Coarse-grained modelings were used to find an optimum design of block copolymer, PEG-b-PEI that would condense DNA and form core-corona structures to provide better biocompatibility.
polyethylenimine molecular dynamics simulations protonation copolymers multiscale modeling
Yongmei Wang Jesse Ziebarth
Department of Chemistry, The University of Memphis, Memphis, Tennessee 38154, USA
国际会议
The First Symposium on Innovative Polymers for Controlled Delivery(新型高分子材料与控制释放国际会议 SIPCD 2010)
苏州
英文
410-412
2010-09-14（万方平台首次上网日期，不代表论文的发表时间）