Development of a Systematic and Extensible Force Field for Peptoids (STEPs)

Abstract

Peptoids (N-substituted glycines) are a class of biomimetic polymers that have attracted significant attention due to their accessible synthesis and enzymatic and thermal stability relative to their naturally occurring counterparts (polypeptides). While these polymers provide the promise of more robust functional materials via hierarchical approaches, they present a new challenge for computational structure prediction for material design. The reliability of calculations hinges on the accuracy of interactions represented in the force field used to model peptoids. For proteins, structure prediction based on sequence and de novo design has made dramatic progress in recent years; however, these models are not readily transferable for peptoids. Current efforts to develop and implement peptoid-specific force fields are spread out, leading to replicated efforts and a fragmented collection of parameterized sidechains. Here, we developed a peptoid-specific force field containing 70 different side chains, using GAFF2 as starting point. The new model is validated based on the generation of Ramachandran-like plots from DFT optimization compared against force field reproduced potential energy and free energy surfaces as well as the reproduction of equilibrium cis/trans values for some residues experimentally known to form helical structures. Equilibrium cis/trans distributions (Kct) are estimated for all parameterized residues to identify which residues have an intrinsic propensity for cis or trans states in the monomeric state.

Influence of Peptoid Sequence on the Mechanisms and Kinetics of 2D Assembly

“…Molecular dynamics (MD) simulations were performed using Gromacs 2020.2 . Structures and force field topologies were built in tleap, utilizing the STEPs force field for peptoids . The missing protonated version of the terminal groups for Peptoid 2 and Peptoid 3 were parametrized and added to the STEPs library.…”

“… 46 Structures and force field topologies were built in tleap, utilizing the STEPs force field for peptoids. 47 The missing protonated version of the terminal groups for Peptoid 2 and Peptoid 3 were parametrized and added to the STEPs library. The hydrophobic core was packed featuring an all-cis backbone and key distances for the inter- and intramolecular phenyl ring distances as discussed by Hammons et al 38 Each membrane consisted of 16 peptoid monomers packed in a four-by-four periodic membrane.…”

Minimal Peptoid Dynamics Inform Self-Assembly Propensity

“…Recently, Harris et al have built on GAFF-φ (also termed GAFF2) extending it to be applicable to 70 peptoid residues. A novel feature of this model is an emphasis on the reproduction of residue specific K cis / trans values, setting a precedent for the incorporation of this peptoid intrinsic property into future parametrization schemes which will in turn enable greater distinction between peptoid models and their their amino acid counterparts …”

Dissipative particle dynamics simulation for peptoid nanosheet with non-empirical parameter set

“…Recently, a special semi-empirical FF set for peptoids has been reported. 11) A coarse-grained (CG) FF has also been proposed for peptoids by modifying the empirical MARTINI set for peptides. 12) In contrast, we have developed an original procedure that performs the dissipative particle dynamics (DPD) 13) simulation of the CG type with non-empirical interparticle interaction (χ) parameters derived from the fragment MO (FMO) method.…”