A modular and extensible CHARMM-compatible model for all-atom simulation of polypeptoids.

Area of Science:

• Polymer Chemistry
• Computational Chemistry
• Materials Science

Background:

• Peptoids (N-substituted glycines) are versatile synthetic polymers with applications in drug delivery, catalysis, and biomimicry.
• Classical molecular simulations, particularly using the CGenFF-NTOID model, are crucial for understanding peptoid behavior.
• Extending existing force fields to new peptoid side chains traditionally requires extensive reparameterization, limiting modularity.

Purpose of the Study:

• To develop a modular extension of the CGenFF-NTOID force field for peptoids.
• To enable direct incorporation of arbitrary side chains from the CHARMM General Force Field (CGenFF).
• To create an extensible modeling paradigm for peptoid simulations.

Main Methods:

• Developed the Modular Side Chain CGenFF-NTOID (MoSiC-CGenFF-NTOID) model by decomposing peptoid backbone and side chain parameterizations.
• Ported arbitrary side chains from the CGenFF force field directly into the peptoid model.
• Validated the MoSiC-CGenFF-NTOID model against ab initio calculations and experimental data.

Main Results:

• Created a validated MoSiC-CGenFF-NTOID model covering all 20 natural amino acid side chains and 13 common synthetic side chains.
• Established an extensible framework for incorporating novel peptoid side chains, determining the need for refitting CGenFF parameters.
• Developed a tool for automated initial structure generation, freely available to the research community.

Conclusions:

• The MoSiC-CGenFF-NTOID model significantly enhances the modularity and extensibility of peptoid molecular simulations.
• This approach streamlines the incorporation of diverse side chains, facilitating broader applications of peptoid research.
• The freely available model and tool empower researchers to efficiently explore novel peptoid sequences and properties.