RESEARCH: CANCER
FOLDING PROJECT #18457 PROFILE

This project relates to designing drugs that target a protein called GABARAP. Researchers created special peptides (small chains of amino acids) that stick tightly to GABARAP, blocking its function in cells. By understanding how these peptides work, scientists hope to develop new cancer treatments.

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.

---

GABARAP

Gamma-aminobutyric acid receptor-associated protein

GABARAP is a protein that plays a role in autophagy, the process of cellular degradation. It's being investigated as a target for cancer therapeutics.

---

Autophagy

The natural process of cells breaking down and recycling their components.

Autophagy is a vital cellular process where cells degrade and recycle damaged parts or unnecessary materials. This helps maintain cell health and function.

---

Stapled Peptides

Synthetic peptides with a covalent bond between specific amino acids, increasing their stability and binding affinity.

Stapled peptides are engineered molecules designed to mimic natural proteins. They have potential as drugs because they can bind tightly to specific targets in the body.

---

LC3

Microtubule-associated protein 1 light chain 3

LC3 is a protein involved in autophagy. It plays a role in forming autophagosomes, the structures that engulf and degrade cellular components.

---

Molecular Simulation

Using computer models to simulate the behavior of molecules and systems.

Molecular simulations help researchers understand how molecules interact and behave. This information is crucial for designing new drugs and materials.

---

Cancer Therapeutics

Treatments aimed at preventing, controlling, or curing cancer.

Cancer therapeutics are medications and therapies used to treat cancer. They can involve surgery, radiation, chemotherapy, or targeted therapies.