Official Project Description
Peptoids (N-substituted oligoglycines) are biomimetic heteropolymers that can be synthesized using a specific sequence of monomers, much like biological protein.
There are many fascinating examples of peptoids that can adopt folded structures in solution, assemble into nanostructures (1), and bind protein targets (2).
In order to computationally design peptoids as therapeutics or for other applications, we need accurate simulation models.
In collaboration with other groups, the Voelz group is working to test the accuracy of peptoid force fields against solution-phase NMR measurements.
Unlike peptides, however, peptoids' amide bonds can populate both cis and trans conformations, and slow transitions between these states make it difficult to sample peptoid folding landscapes using molecular simulation. This project is designed to test enhanced sampling methods for overcoming cis/trans isomerization barriers.
The results of this study will inform our ongoing work in peptoid force field evaluation. References 1.
Sun, Jing, and Ronald N.
Zuckermann.
“Peptoid Polymers: A Highly Designable Bioinspired Material.” ACS Nano 7, no.
6 (June 25, 2013): 4715–32.
https://doi.org/10.1021/nn4015714. 2.
Schneider, Jeffrey A., Timothy W.
Craven, Amanda C.
Kasper, Chi Yun, Michael Haugbro, Erica M.
Briggs, Vladimir Svetlov, et al.
“Design of Peptoid-Peptide Macrocycles to Inhibit the β-Catenin TCF Interaction in Prostate Cancer.” Nature Communications 9, no.
1 (December 2018): 4396.