(63f) Developing Predictive Models for Peptoids

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 and resistant to protease degradation [2], and peptoid sequences can be synthesized using more than 300 commercially available amines [1], [3], making peptoids versatile and appealing compounds for combinatorial materials design. Additionally, peptide backbones don’t have hydrogen bonding making developing peptoid models less challenging than developing models for their peptide counterparts.

The goal of this project is to develop predictive coarse-grained models for peptoids that can be used for in silico combinatorial design. This will be achieved in two stages: (1) Development of a model for the peptoid backbone that can reproduce its structural properties under different conditions, and (2) Development of models for a library of side chains that can later be used for combinatorial design. We will start by developing atomistic models using the OPLS force field with missing parameters fit to ab initio calculations. The models will then be fine-tuned to reproduce experimental structure data.

We will present models of peptoids with simple side chains. Atomistic simulations will be used to develop coarse-grained models. Our models will be tuned to accurately reproduce structural properties obtained by NMR measurements, and compared to available literature data. In future work, we will determine interaction potentials for other peptoid side-chains. These models will serve as starting points in developing predictive 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, and C. J. Kirkpatrick,  Comp Biomaterials. 2, 53 (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, Nature materials. 9, 454 (2010)

[3]      R. N. Zuckerman, S. B. H. Kent, and W. H. Moost. J. Am. Chem. Soc. 6, 10646 (1992)