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

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.