Branched polyethyleneimine: CHARMM force field and molecular dynamics simulations

Area of Science:

• Computational Chemistry
• Biomolecular Modeling
• Materials Science

Background:

• Polyethyleneimine (PEI) is a promising non-viral vector for gene delivery.
• Accurate molecular simulations require reliable force fields (FFs) that capture polymer behavior.
• Existing FFs for PEI primarily focus on linear forms, limiting simulations of branched PEI.

Purpose of the Study:

• To develop and validate an all-atom CHARMM force field for branched polyethyleneimine (PEI).
• To enable accurate atomistic simulations of branched PEI properties and DNA complexation.
• To provide insights into optimal conditions for DNA-PEI complex formation in gene delivery.

Main Methods:

• Extension of a previously published CHARMM FF for linear PEI to include branched configurations.
• Introduction of a new residue type for branch connectors, with parameters derived from ab initio calculations.
• Extensive molecular dynamics simulations of solvated branched PEIs and their complexes with DNA.

Main Results:

• The validated FF accurately reproduces structural properties (gyration radii, end-to-end distances) and dynamics (diffusion coefficients) of branched PEIs.
• Comparison with linear PEIs highlights differences in behavior influenced by branching.
• Simulations reveal favorable attachment conformations for DNA-PEI complexes.

Conclusions:

• The developed atomistic force field is suitable for simulating PEI with diverse branching, protonation, and sizes.
• This tool is expected to yield significant insights into optimizing DNA-PEI complex formation for gene delivery applications.
• The study advances the computational modeling capabilities for non-viral gene delivery vectors.