Polyethyleneimine (PEI), one of the most widely used nonviral gene carriers, was investigated in the presented work at coarse‐grained (CG) level. The main focus was on elaborating a realistic CG force field (FF) aimed to reproduce dynamic structural features of protonated PEI chains and, furthermore, to enable massive simulations of DNA–PEI complex formation and condensation. We parametrized CG Martini FF models for PEI in polarizable and nonpolarizable water by applying Boltzmann inversion techniques to all‐atom (AA) probability distributions for distances, angles, and dihedrals of entire monomers. The fine‐tuning of the FFs was achieved by fitting simulated CG gyration radii and end‐to‐end distances to their AA counterparts. The developed Martini FF models are shown to be well suited for realistic large‐scale simulations of size/protonation‐dependent behavior of solvated PEI chains, either individually or as part of DNA–PEI systems. © 2019 Wiley Periodicals, Inc.

e present a revised version of our previously published atomistic Chemistry at Harvard Macromolecular Mechanics (CHARMM) force field for polyethyleneimine (PEI). It is based on new residue types (with symmetric C N C backbone), whose integer charges and bonded parameters are derived from ab initio calculations on an enlarged set of model polymers. The force field is validated by extensive molecular dynamics simulations on solvated PEI chains of various lengths and protonation patterns. The profiles of the gyration radius, endto-end distance, and diffusion coefficient fine-tune our previous results, while the simulated diffusion coefficients excellently reproduce experimental findings. The developed CHARMM force field is suitable for realistic atomistic simulations of size/ protonation-dependent behavior of PEI chains, either individually or composing polyplexes, but also provides reliable allatom distributions for deriving coarse-grained force fields for PEI.

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