Towards a coarse-grained model of the peptoid backbone: the case of N,N-dimethylacetamide

Abstract

In this study, a coarse-grained (CG) model for N,N-dimethylacetamide (DMA), which represents the polypeptoid backbone, is developed as a step towards establishing a CG model of the complex polypeptoid system. Polypeptoids or poly N-substituted glycines are a type of peptidomimetic polymers that are highly tunable, and hence an ideal model system to study self-assembly as a function of chemical groups in aqueous soft matter systems. The DMA CG model is parameterized to reproduce the structural properties of DMA liquid as well as a dilute aqueous solution of DMA using a reference all atom model, namely the OPLS-AA force-field. The intermolecular forces are represented by the Stillinger-Weber potential, that consists of both two- and three-body terms that are very short-ranged. The model is validated on thermodynamic properties of liquid and aqueous DMA, as well as the vapor-liquid interface of liquid DMA and the structure of a concentrated aqueous solution of DMA in water as well as a simple peptoid in water. Without long-ranged interactions and the absence of interaction sites on hydrogen atoms, the CG DMA model is an order of magnitude faster than the higher resolution all-atom (AA) model.

MARTINI-Compatible Coarse-Grained Model for the Mesoscale Simulation of Peptoids

“…Du, Rick, and Kumar developed a CG model of polysarcosine (poly(N-methyl glycine), N,N-dimethylacetamide) as a prototypical model for the polypeptoid backbone. 26 The optimized potential for liquid simulations-united atom (OPLS-UA) model is adopted for the intramolecular peptoid interactions that explicitly models all atoms except hydrogens, which are eliminated. 29 The water solvent is modeled using Molinero and co-worker's model of water (mW) that models each water molecule as a single bead that interacts via a short-ranged Stillinger−Weber potential comprising two-and three-body terms.…”

Hierarchical assemblies of polypeptoids for rational design of advanced functional nanomaterials

“…[ 50 ] A number of more computationally efficient coarse grained models have been developed to access these time and length scales. [ 31,51–53 ] The coarse‐grained peptoid models are developed in a bottom‐up way based on the atomistic peptoid simulations. However, one of the biggest shortcomings for the coarse‐grained models is nontransferable, which require huge effort in development of coarse‐grained models.…”

Simulation studies of polypeptoids using replica exchange with dynamical scaling and dihedral biasing

“…In this manuscript, we describe a new RE method for sampling the amide dihedral degrees of freedom and apply it to two different peptoid oligomers, as shown in Figure 1. N‐(methyl) glycine, or sarcosine, is the most commonly studied polypeptoid 12,13,18–20,22,24–26 . N‐ethyl glycine was chosen as a more hydrophobic polypeptoid.…”

“…N-(methyl) glycine, or sarcosine, is the most commonly studied polypeptoid. 12,13,[18][19][20]22,[24][25][26] N-ethyl glycine was chosen as a more hydrophobic polypeptoid.…”