<i>In Silico</i> Structural Comparison of Aromatic and Aliphatic Chiral Peptoid Oligomers

Atomistic simulations of peptoids have the capability to predict structure-property relationships, depending on the accuracy of the associated force field. This work presents an addendum to the CGenFF-NTOID peptoid force field for aliphatic side chains. We develop parameters for two aliphatic side chains, R_<i>N</i>1-tertiary butylethyl glycine (<i>r1tbe</i>) and S_<i>N</i>1-tertiary butylethyl glycine (<i>s1tbe</i>). Enhanced sampled (well-tempered metadynamics) atomistic simulations are performed using CGenFF-NTOID to determine the monomer structural preferences for these side chains. The free energy minima attained through these simulations are compared with structural observations obtained from experiments. We also compare the structural preferences of aliphatic <i>s1tbe</i> and aromatic S_<i>N</i>1-naphthylethyl glycine (<i>s1ne</i>). This is done through parallel bias metadynamics on monomers and pentamers of <i>s1tbe</i> and <i>s1ne</i>. The structural observations through simulations are also compared with available experimental metrics of the dihedral angles and pitch. The pentamer minima structures are also compared with <i>ab initio</i> optimized structures, which show excellent agreement. This comparison illustrates alternatives to aromatic side chains that can be used to stabilize peptoid secondary structures. The developed parameters help to increase the diversity of peptoid side chains available for materials discovery through computational studies.