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

Abstract

Peptoids (poly-N-substituted glycines) are a class of synthetic polymers that are regioisomers of peptides (poly-C-substituted glycines), in which the point of side-chain connectivity is shifted from the backbone C to the N atom. Peptoids have found diverse applications as peptidomimetic drugs, protein mimetic polymers, surfactants, and catalysts. Computational modeling is valuable in the understanding and design of peptoid-based nanomaterials. In this work, we report the bottom-up parameterization of coarse-grained peptoid force fields based on the MARTINI peptide force field against all-atom peptoid simulation data. Our parameterization pipeline iteratively refits coarse-grained bonded interactions using iterative Boltzmann inversion and nonbonded interactions by matching the potential of mean force for chain extension. We assure good sampling of the amide bond cis/trans isomerizations in the all-atom simulation data using parallel bias metadynamics. We develop coarse-grained models for two representative peptoidspolysarcosine (poly­(N-methyl glycine)) and poly­(N-((4-bromophenyl)­ethyl)­glycine)and show their structural and thermodynamic properties to be in excellent accord with all-atom calculations but up to 25-fold more efficient and compatible with MARTINI force fields. This work establishes a new rigorously parameterized coarse-grained peptoid force field for the understanding and design of peptoid nanomaterials at length and time scales inaccessible to all-atom calculations.

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

“…Peptoids have not been studied with theoretical methods in the context of their membrane activity, but rather in the context of their applications in nanotechnology, e.g., the study by Jin et al, in 2016 [838]. Recently, a coarse-grained force-field created within the MARTINI framework [605] for peptoids was developed [839]. Nevertheless, the interactions between peptoids and membranes have been investigated experimentally [840].…”

The Martini Model in Materials Science

“…[ 264 ] The simulations showed that DMAP molecules interfere with the monomer‐monomer interactions at the fiber ends by first penetrating in between the monomer porphyrin cores and then facilitating monomer dissociation from the fiber end. [ 264 ] Other supramolecular material systems that have been simulated with Martini include supramolecular block copolymers, [ 267,268 ] peptide‐based supramolecular polymers chemically linked to spiropyran‐based networks, [ 269 ] poly‐catenanes, [ 270 ] peptoid‐based nanomaterials, [ 271 ] supramolecular macrocycle fibers, [ 272 ] responsive conjugated polymers, [ 273 ] platinum complexes, [ 274,275 ] supramolecular polymer hydrogels, [ 276 ] and light‐harvesting double‐walled nanotubes. [ 277 ]…”

Bio-instructive materials on-demand – combinatorial chemistry of peptoids, foldamers, and beyond

“…3,4,6,9,58 Based on various sequence-structure analyses, nowadays, both the rational design and the computer-aided structure prediction of peptoid foldamers is possible. 1,5,115,[130][131][132][133][134]…”