(144e) Developing Peptoid Models Using Atomistic Simulations

Peptoids (poly-n-substituted glycines) are peptide-like macromolecules composed of modified glycine units which have side chains attached to the nitrogen atoms [1]. Peptoids are biocompatible, resistant to protease degradation [2], and they can be synthesized using more than 300 commercially available amines [1], [3]. This makes peptoids versatile and appealing compounds for combinatorial materials design. Additionally, peptoid backbones do not have internal hydrogen bonding, and so developing peptoid models is less challenging than developing models for their peptide counterparts.

This project uses atomistic simulations to investigate the relationship between peptoid side-chains and the peptoid backbone secondary structure. We use force-field parameters from the Generalized CHARMM Force Field (GCFF), fitting missing parameters using ab initio calculations as needed. Using this peptoid-specific force-field, we generate Ramachandran-type probability plots describing the dihedrals of the peptoid backbone. We find such plots for a variety of peptoid side chains, and compare their distributions to experimentally documented peptoid structures.

These atomistic simulations will serve as a starting point in developing predictive coarse-grained models for the combinatorial design of more complex peptoid sequences.

References:

[1]      J. Seo, B. Lee, Z. R. N. P. Synthesis, N. I. P. Ducheyne, K. E. Healy, D. W. Hutmacher, D. W. Grainger, C. J. Kirkpatrick, and C. Biomaterials, “Peptoids: Synthesis, Characterization, and Nanostructures,” Comprehensive Biomaterials, vol. 2, pp. 53–76, 2011.

[2]      K. T. Nam, S. a Shelby, P. H. Choi, A. B. Marciel, R. Chen, L. Tan, T. K. Chu, R. a Mesch, B.-C. Lee, M. D. Connolly, C. Kisielowski, and R. N. Zuckermann, “Free-floating ultrathin two-dimensional crystals from sequence-specific peptoid polymers.,” Nature materials, vol. 9, no. 5, pp. 454–60, May 2010.

[3]      R. N. Zuckerman, S. B. H. Kent, and W. H. Moost, “Efficient Method for the Preparation of Peptoids [Oligo(N-substituted glycines)],” no. 6, pp. 10646–10647, 1992.