RESEARCH: CANCER
FOLDING PROJECT #16483 PROFILE

Cancer often involves multiple malfunctioning proteins. The project focuses on Menin, a protein involved in hormone production and cell regulation. Researchers are using computer simulations to study how small molecules can inhibit Menin and how mutations in Menin affect its ability to bind these inhibitors. This could lead to new treatments for endocrine gland tumors.

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 found within the cell's nucleus. It plays a vital role in controlling how cells communicate with each other (cell signaling) and which genes are turned on or off (gene expression). This makes Menin important for regulating many cellular processes, including growth and development.

Small-molecules

Molecules with a relatively small size that can bind to specific target proteins.

Small molecules are compounds of limited size used in medicine and research. They often function as drugs by binding to specific proteins in the body, influencing their activity. These interactions can be used to treat diseases or study cellular processes.

Mutations

Permanent changes in the DNA sequence of a gene.

Mutations are alterations in the genetic code that can affect how proteins function. They can occur spontaneously or be induced by environmental factors like radiation. In cancer, mutations often lead to uncontrolled cell growth and proliferation.

AlphaFold

An artificial intelligence system for predicting protein structures.

AlphaFold is a groundbreaking AI tool that can predict the three-dimensional shapes of proteins with remarkable accuracy. This has revolutionized research by providing crucial insights into how proteins function and interact.