RESEARCH: CANCER
FOLDING PROJECT #16479 PROFILE

This project studies Menin, a protein important for controlling cell growth in hormone-producing glands. Researchers are using computer models to understand how small molecules can block Menin's activity and how mutations in Menin affect this interaction. This knowledge could lead to new cancer treatments.

In cancer treatment it is common to target multiple different putative proteins, because multiple proteins can malfunction in tumors to drive cancer.

One such protein, particularly known to be important in endocrine gland tumors (the places where hormones are secreted), is Menin-1 (Menin).

Menin is a protein found in the nucleus protein and plays a key role in regulating cell-signaling and gene expression (which genes turn on and off).

While the explicit details of Menin's behavior are not known, targeting it's inhibition with small-molecules (ligands) has demonstrated promising potential in blocking tumor growth.

However, like with many disease, mutations within Menin can *also* counteract this ligand-binding behavior.

Therefore, it is not just important to study how Menin works, or how to target it with small molecules, but also how mutations impact Menin-Ligand interactions.

This set of projects seeks to answer the latter two questions - how do small molecules inhibit Menin and how do mutations within Menin alter small-molecule affinity.

In projects 16472 & 16473, we simulate Menin by itself and Menin bound to a known small molecule inhibitor that is shown to treat tumors in patients! Thanks to the powerhouse efforts at cataloguing cancer mutations at Memorial Sloan-Kettering, we also know of 3 mutations that impact the ability of Menin to bind this inhibitor.

Projects 16474–16483 simulate either a) each of these Menin mutants or b) Menin mutants bound to this inhibitor. Bonus: Some of these structures are being simulated with the help of the AlphaFold database!.

Menin

A protein found in the nucleus that regulates cell signaling and gene expression.

Menin is a crucial protein located inside the cell's nucleus. It plays a vital role in controlling how cells communicate with each other and which genes are turned on or off. Researchers are particularly interested in Menin because it can be affected by mutations, potentially contributing to the development of cancer.

Small-molecules

Molecules used in medications to target specific biological processes.

Small-molecules are tiny chemical compounds that can interact with and influence biological processes within the body. In medicine, they're often used as drugs to treat diseases like cancer by targeting specific proteins or pathways involved in disease development.

Ligands

Molecules that bind to specific proteins, often with a therapeutic effect.

Ligands are molecules that have a strong attraction to other molecules, like proteins. In medicine, they're often designed to specifically bind to disease-causing proteins, blocking their harmful activity or triggering beneficial effects.

Mutations

Permanent alterations in the DNA sequence of a gene.

Mutations are changes that occur in our DNA, the instruction manual for our cells. These changes can be caused by various factors and sometimes lead to diseases like cancer. In cancer, mutations often disrupt normal cellular processes, allowing uncontrolled growth and spread.

AlphaFold

A deep learning algorithm for predicting protein structures.

AlphaFold is a powerful computer program that uses artificial intelligence to predict the 3D shapes of proteins. This information is crucial for understanding how proteins function and designing new drugs.