title: Development and use of an atomistic CHARMM-based forcefield for peptoid simulation.
abstract: Peptoids are positional isomers of peptides: peptoid sidechains are attached to backbone nitrogens rather than α-carbons. Peptoids constitute a class of sequence-specific polymers resistant to biological degradation and potentially as diverse, structurally and functionally, as proteins. While molecular simulation of proteins is commonplace, relatively few tools are available for peptoid simulation. Here, we present a first-generation atomistic forcefield for peptoids. Our forcefield is based on the peptide forcefield CHARMM22, with key parameters tuned to match both experimental data and quantum mechanical calculations for two model peptoids (dimethylacetamide and a sarcosine dipeptoid). We used this forcefield to demonstrate that solvation of a dipeptoid substantially modifies the conformations it can access. We also simulated a crystal structure of a peptoid homotrimer, H-(N-2-phenylethyl glycine)3 -OH, and we show that experimentally observed structural and dynamical features of the crystal are accurately described by our forcefield. The forcefield presented here provides a starting point for future development of peptoid-specific simulation methods within CHARMM.
authors.affiliation: Molecular Foundry, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California, 94720.
authors.forename: Dina T
authors.initials: DT
authors.lastname: Mirijanian
authors.forename: Ranjan V
authors.initials: RV
authors.lastname: Mannige
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Zuckermann
authors.forename: Stephen
authors.initials: S
authors.lastname: Whitelam
mesh_terms: D056004:Molecular Dynamics Simulation; D034444:Peptoids / Q000737:chemistry*; D011487:Protein Conformation; D011789:Quantum Theory; D012984:Software
chemical_list: D034444:Peptoids
keywords: CHARMM; forcefield; parameterization; peptoid; simulation