RESEARCH: CANCER
FOLDING PROJECT #18427 PROFILE

Researchers created special peptides that block GABARAP, a protein important for cell recycling (autophagy). By studying how these peptides bind to GABARAP, the project aims to design new drugs that target cancer. This research could lead to better ways to treat cancer by disrupting autophagy in tumor cells.

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

GABARAP (Gamma-aminobutyric acid receptor-associated protein) is a protein receptor involved in pathways that regulate autophagy, a type of cell degradation.

The Kritzer lab has recently developed stapled peptide inhibitors that strongly bind to GABARAP and its closely related protein receptor LC3 (Brown 2022).

These simulations are designed to examine the roles that peptide sequence and conformational preorganization in solution play in determining binding affinity.

This work will help us understand better ways of performing molecular simulation-based molecular design, with applications toward cancer therapeutics. Reference Brown, Hawley, Mia Chung, Alina Üffing, Nefeli Batistatou, Tiffany Tsang, Samantha Doskocil, Weiqun Mao, et al.

“Structure-Based Design of Stapled Peptides That Bind GABARAP and Inhibit Autophagy.” Journal of the American Chemical Society 144, no.

32 (August 17, 2022): 14687–97.

https://doi.org/10.1021/jacs.2c04699.

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GABARAP

Gamma-aminobutyric acid receptor-associated protein

GABARAP is a protein that plays a role in autophagy, a process where cells break down and recycle old components. It interacts with other proteins to control this process.

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LC3

Microtubule-associated protein 1 light chain 3

LC3 is a protein involved in autophagy. It attaches to damaged cellular components and helps form autophagosomes, which are structures that engulf and degrade these components.

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Stapled Peptide Inhibitors

Synthetic peptides designed to bind to specific proteins and inhibit their function.

Stapled peptide inhibitors are a type of drug that works by blocking the activity of specific proteins. They are being investigated as potential treatments for various diseases, including cancer.

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Autophagy

A process by which cells break down and recycle their own components.

Autophagy is a natural process that allows cells to clean up damaged or unnecessary parts. It plays a role in maintaining cellular health and responding to stress.

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Molecular Simulation

Computer-based simulations of molecular interactions and processes.

Molecular simulations are used to study how molecules interact with each other. This information can be used to design new drugs and materials.

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Cancer Therapeutics

The treatment of cancer.

Cancer therapeutics encompasses a wide range of treatments aimed at preventing, controlling, or curing cancer. This includes surgery, chemotherapy, radiation therapy, and immunotherapy.