RESEARCH: CANCER
FOLDING PROJECT #18428 PROFILE

Researchers made peptides that block GABARAP and LC3 proteins. These proteins control how cells break down themselves (autophagy). Blocking them could help fight cancer. The project relates to understanding how peptide design affects their binding strength, which can be used to create better drugs.

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 interacts with GABA receptors and plays a role in autophagy, a cellular process for degrading and recycling cellular components. It's being researched as a target for drug development in cancer.

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Autophagy

A process of cellular degradation and recycling

Autophagy is a natural process within cells where damaged or unnecessary components are broken down and recycled. This process is essential for maintaining cell health and plays a role in various diseases.

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LC3

Microtubule-associated protein 1A/1B-light chain 3

LC3 is a protein involved in autophagy. It helps form structures called autophagosomes, which engulf cellular waste and deliver it to lysosomes for degradation.

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Stapled Peptide Inhibitors

Peptides with a chemical modification that enhances their stability and binding affinity to target proteins

Stapled peptides are designed drug molecules based on short chains of amino acids. They have a 'staple' bond that makes them more stable and effective at blocking specific proteins.

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Molecular Simulation

A computer-based method for modeling and predicting the behavior of molecules

Molecular simulations use mathematical models to simulate how atoms and molecules interact. This helps researchers understand chemical reactions, protein folding, and drug interactions.

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Cancer Therapeutics

Treatments for cancer

Cancer therapeutics encompass various approaches to treating cancer, including chemotherapy, radiation therapy, immunotherapy, and targeted therapies.