RESEARCH: CANCER
FOLDING PROJECT #16472 PROFILE

This project studies Menin, a protein involved in cancer growth. Researchers are using computer simulations to understand how drugs block Menin and how changes in the Menin protein affect drug binding. This could lead to better 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 gene expression and cell signaling.

Menin is a crucial protein located within the cell's nucleus. It plays a vital role in controlling how genes are turned on and off (gene expression) and in regulating cellular communication (cell-signaling). Disruptions to Menin function have been linked to the development of certain cancers, particularly endocrine gland tumors.

Ligands

Molecules that bind to specific target proteins.

Ligands are molecules designed to attach themselves to specific targets, often proteins. In drug development, ligands can be used as therapeutic agents. For example, small-molecule ligands can be designed to block the activity of disease-causing proteins, like those involved in cancer growth.

Mutations

Permanent alterations in the DNA sequence.

Mutations are changes that occur in our DNA sequence. These alterations can affect how genes function and sometimes lead to disease. In cancer research, mutations play a crucial role as they can drive uncontrolled cell growth and tumor formation.

AlphaFold

A powerful artificial intelligence system for predicting protein structures.

AlphaFold is a revolutionary AI program developed by DeepMind that excels at predicting the 3D shapes of proteins. This ability to accurately model protein structures has immense implications for understanding how proteins function and designing new drugs.