RESEARCH: CANCER
FOLDING PROJECT #16473 PROFILE

This project studies Menin, a protein important for controlling cell growth that's often involved in cancer. Scientists are looking at how drugs block Menin and how mutations in Menin affect this process. They're using computer simulations to understand these interactions better.

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

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!.

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Menin

A protein found in the nucleus that regulates gene expression.

Menin is a crucial protein located inside cells' nuclei. It controls which genes are switched on or off, influencing how cells function. In cancer, Menin malfunctions can drive tumor growth.

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Protein

Large biomolecules essential for all biological processes.

Proteins are the building blocks of life. They carry out a vast array of functions in living organisms, from transporting molecules to catalyzing chemical reactions.

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Nucleus

The membrane-bound organelle containing the cell's genetic material (DNA).

The nucleus is like the control center of a cell. It houses the DNA, which contains the instructions for building and maintaining the organism.

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Gene Expression

The process by which information encoded in DNA is used to synthesize proteins.

Gene expression is the way our DNA instructions are turned into functional products like proteins. This process is essential for all life.

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Tumor

An abnormal mass of tissue that results from uncontrolled cell growth.

A tumor is a clump of cells that divides uncontrollably. While some tumors are benign (non-cancerous), others are malignant (cancerous) and can spread to other parts of the body.

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Ligand

A molecule that binds to a specific receptor or protein.

Ligands are molecules that fit into specific receptors like keys in locks. This binding can trigger various cellular responses, including those targeted by drugs.

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Mutation

A permanent change in the DNA sequence.

Mutations are changes in our genetic code. While some mutations are harmless, others can disrupt normal cell function and contribute to diseases like cancer.

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AlphaFold

A deep learning algorithm for predicting protein structures.

AlphaFold is a powerful AI tool that can predict the 3D shape of proteins. This knowledge is crucial for understanding how proteins function and developing new drugs.