RESEARCH: CANCER
FOLDING PROJECT #16482 PROFILE

This project investigates how drugs work against cancer by studying a protein called Menin, which is often involved in hormone-producing tumors. Researchers will simulate Menin both alone and bound to a drug that shows promise in treating patients. They'll also look at how changes (mutations) in the Menin protein affect its ability to bind the drug.

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-1

A tumor suppressor protein involved in cell growth and development.

Menin-1 is a protein crucial for regulating gene expression and cell signaling. It's often found mutated in endocrine gland tumors, hindering its normal function. Scientists are studying how to target Menin-1 with drugs to stop tumor growth.

Endocrine Gland Tumors

Tumors that arise in glands responsible for producing and releasing hormones.

Endocrine gland tumors develop in tissues that produce hormones, like the thyroid or adrenal glands. These tumors can disrupt hormone production, leading to various health problems.

Mutations

Permanent changes in the DNA sequence.

Mutations are alterations in our genes that can affect how cells function. In cancer, mutations often disrupt normal cell growth and division, leading to tumor formation.

Small Molecules

Organic compounds with a relatively low molecular weight used as drugs or drug candidates.

Small molecules are chemical substances that can interact with biological targets, like proteins. They are frequently used in drug development to treat various diseases.

Ligands

Molecules that bind to specific receptors or target proteins.

Ligands are molecules that attach to specific sites on proteins, often triggering a biological response. They play a crucial role in cell signaling and drug action.

AlphaFold

A deep learning algorithm for predicting the three-dimensional structure of proteins.

AlphaFold is an advanced computer program that can accurately predict the shapes of proteins. This helps researchers understand how proteins function and design new drugs.