Development and use of an atomistic CHARMM-based forcefield for peptoid simulation.

Area of Science:

• Biomolecular simulation
• Polymer chemistry
• Computational chemistry

Background:

• Peptoids are peptide isomers with side chains on backbone nitrogens, offering resistance to degradation and structural diversity.
• Molecular simulation tools for peptoids are limited, hindering their study compared to proteins.

Purpose of the Study:

• To present a first-generation atomistic forcefield for peptoid simulation.
• To provide a foundation for developing advanced peptoid-specific simulation methods within the CHARMM framework.

Main Methods:

• Adapted the CHARMM22 peptide forcefield.
• Tuned parameters using experimental data and quantum mechanical calculations for model peptoids.
• Simulated solvated dipeptoids and a peptoid homotrimer crystal structure.

Main Results:

• The new forcefield accurately describes experimental and quantum mechanical data for model peptoids.
• Solvation significantly impacts dipeptoid conformations.
• Simulations of a peptoid homotrimer crystal structure reproduce experimental features.

Conclusions:

• The developed forcefield is a crucial starting point for peptoid molecular simulations.
• This work facilitates deeper understanding of peptoid structural and dynamic properties.
• Enables future advancements in peptoid-based materials and therapeutics.