RESEARCH: CANCER
FOLDING PROJECT #12462 PROFILE

Peptoids are man-made molecules that act like proteins. This project uses computer simulations to study how peptoids fold and interact with other molecules. This is important because it could help us design new drugs and materials.

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; synthetic polymers mimicking proteins.

Peptoids are synthetic molecules designed to mimic the structure and function of proteins. They are made up of repeating units called monomers, linked together like a chain. Peptoids can fold into complex shapes, bind to other molecules, and have potential applications in medicine and materials science.

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Oligoglycines

Short chains of amino acids glycine.

Oligoglycines are short chains of the amino acid glycine. Glycine is the simplest amino acid and has a basic structure with only a hydrogen atom as its side chain. Oligoglycines can be used to build larger molecules like peptides and proteins.

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Monomers

Basic building blocks of polymers.

Monomers are the basic building blocks of polymers. They are small molecules that can link together to form long chains called polymers. In biology, monomers like amino acids are used to build proteins.

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Proteins

Large biomolecules essential for life.

Proteins are large complex molecules that play many vital roles in living organisms. They are made up of chains of amino acids folded into specific 3-dimensional shapes. Proteins carry out a wide variety of functions, including catalyzing chemical reactions, transporting molecules, providing structural support, and defending against disease.

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NMR

Nuclear Magnetic Resonance

NMR is a powerful analytical technique used to study the structure and dynamics of molecules. It works by exploiting the magnetic properties of atomic nuclei.

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Force Field

Mathematical model used to describe molecular interactions.

A force field is a mathematical model that describes how atoms and molecules interact with each other. It's used in computer simulations to predict the behavior of molecules.

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Cis/Trans Isomerization

Conformational change in molecules.

Cis/trans isomerization is a type of conformational change where molecules can exist in two different arrangements. The 'cis' and 'trans' configurations refer to the spatial arrangement of atoms around a double bond.

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Peptoid Force Field

Mathematical model specific to peptoids.

A peptoid force field is a specialized mathematical model used to describe how peptoid molecules interact with each other. It's essential for accurately simulating the behavior of these synthetic polymers.