Polyethyleneimine (PEI), one of the non-viral vectors of great interest for gene delivery, was investigated at all-atom level, with particular emphasis on its branched form. We report the extension of our previously published CHARMM force field (FF) for linear PEI, with parameters optimized specifically for branched configurations. A new residue type for the branch connector is introduced and the charges and bonded parameters are derived from ab initio calculations based on a model polymer. The new FF is validated by extensive molecular dynamics simulations of solvated branched PEIs of various protonation fractions and branch lengths. The gyration radii, end-to-end distances, and diffusion coefficients are compared with results for linear PEIs of similar molecular weights and protonation patterns. Solvated complexes of DNA with (linear/branched) PEI were also investigated to determine favorable attachment conformations. The parametrized atomistic force field is suitable for simulations of PEI with arbitrary branching pattern, protonation, and size, and is expected to provide relevant insights regarding optimal conditions for DNA-PEI complex formation.

中文翻译：

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支化聚乙烯亚胺：CHARMM 力场和分子动力学模拟

聚乙烯亚胺 (PEI) 是一种对基因传递非常感兴趣的非病毒载体，在全原子水平上进行了研究，特别强调其分支形式。我们报告了我们之前发布的用于线性 PEI 的 CHARMM 力场 (FF) 的扩展，其中的参数专门针对分支配置进行了优化。引入了分支连接器的新残基类型，电荷和键合参数来自基于模型聚合物的从头计算。新的 FF 通过对各种质子化分数和支链长度的溶剂化支链 PEI 的广泛分子动力学模拟进行验证。将回转半径、端到端距离和扩散系数与具有相似分子量和质子化模式的线性 PEI 的结果进行比较。还研究了 DNA 与（线性/分支）PEI 的溶剂化复合物以确定有利的附着构象。参数化原子力场适用于模拟具有任意分支模式、质子化和大小的 PEI，有望为 DNA-PEI 复合物形成的最佳条件提供相关见解。