Understanding Self-Assembly of Peptoids with Classical Molecular Dynamics Simulations

Peptoids – N-substituted glycines – are a novel biomimetic polymer with numerous applications as drugs and drug delivery agents, scaffold material and nucleation agents. Recent experimental research uncovered that chains of N-ethylcarboxylate – N-ethylphenylchloryl (Nce-Npe) peptoids can aggregate in a calcium chloride electrolyte solution and form nanofibers in the presence of a mica surface. It was also found that calcium ions can affect the equilibrium structure these peptoids [1]. We investigate the solution-state behavior of these peptoids using classical molecular dynamics simulations.

We setup several systems of varying size and ion concentration and run these simulations using a three-site water model and an AMBER99sb-ildn forcefield optimized to describe peptoid systems more accurately. We find that aromatic pi-stacking and ion bridging drive clustering between these peptoids. We also observe the rate of aggregation increases and ion bridging dominates in the presence of Ca²⁺.

These simulations are essential to understanding the self-assembly of peptoids and similar polymers in complex environments.

References:

[1] Daily, M. D., et al., “Divalent Ion Parameterization Strongly Affects Conformation and Interactions of an Anionic Biomimetic Polymer,” J. Phys. Chem. B, 120 (9), pp. 2198-2208 (2016).