RESEARCH: CANCER
FOLDING PROJECT #12463 PROFILE

Peptoids are synthetic molecules that mimic proteins. They can fold and bind to other molecules, making them useful for medicine. The project aims to improve computer simulations of peptoids by overcoming challenges related to their unique structure.

Note: This TLDR is a simplication and may not be 100% accurate.

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.

https://doi.org/10.1038/s41467-018-06845-3.

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Peptoids

N-substituted oligoglycines, biomimetic polymers.

Peptoids are synthetic molecules designed to mimic the structure and function of proteins. They have potential applications in drug development, materials science, and other fields due to their unique properties.

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Oligoglycines

Short chains of amino acids with substitutions on the nitrogen atoms.

Oligoglycines are small chains of amino acids where the nitrogen atoms are modified. These modifications can alter their properties compared to natural proteins, making them useful for various applications.

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Biomimetic

Mimicking the structure or function of biological systems.

Biomimetic refers to the design or creation of materials or processes that imitate natural systems. This approach often draws inspiration from biological structures and functions for enhanced performance.

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Force Fields

Mathematical models that describe the interactions between atoms in molecules.

Force fields are computational tools used to simulate the behavior of molecules. They represent the forces acting between atoms based on their positions and types, allowing researchers to predict molecular properties and interactions.

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NMR

Nuclear Magnetic Resonance

NMR is a powerful technique used to determine the structure and dynamics of molecules. It relies on the magnetic properties of atomic nuclei to provide detailed information about molecular conformation and interactions.

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Cis/Trans Isomerization

The interconversion between cis and trans conformations of a molecule.

Cis/trans isomerization describes the process where a molecule can exist in two different spatial arrangements. This occurs due to rotation around a bond, leading to variations in molecular shape and properties.