RESEARCH: CANCER
FOLDING PROJECT #18117 PROFILE

This project studies KRas, a protein that controls cell growth and is often mutated in cancer. Scientists are using computer simulations to understand how drugs can block KRas activity and treat these cancers. All data and findings will be publicly available.

We are simulating publicly available protein and small molecule structures of the currently very hot cancer target KRas, see https://www.fiercepharma.com/pharma/amgen-s-lumakras-becomes-first-fda-approved-kras-inhibitor-for-lung-cancer-patients for recent developments.

Folding@home has previously looked at this protein (in project 10490), and the following part of the description is copied from there: This project is "studying a small protein called KRAS, which forms a key link in growth signaling and cancer.

This gene is something like a molecular switch with a timer.

When it is bound to a molecule called GDP, it is off, and does not signal that the cell should grow.

However, other proteins can cause it to swap its GDP for a GTP, turning KRAS on.

In the on state, it signals that the cell should grow and divide.

Normally, after some time, KRAS, with the aid of some partners, will chemically convert its GTP to GDP and return to its inactive state. In many cancers, this protein becomes mutated, and cannot return to its off state.

The result? The cells continue to divide without limit.

What’s worse, cancers with this protein mutated tend to have much poorer prognoses.

As a result, scientists have been trying to target this protein for decades." We are investigating the dynamic behavior of KRas with these publicly disclosed inhibitors so that we can apply this knowledge to our own drug design.

At the same time, we are further testing the adaptive sampling methodology.

All data is being made publicly available at https://console.cloud.google.com/storage/browser/stxfah-bucket, and insights from methodology developments will be shared.

This is a project run by Roivant Sciences (formerly Silicon Therapeutics) as was officially announced in this press release: https://foldingathome.org/2021/04/20/maximizing-the-impact-of-foldinghome-by-engaging-industry-collaborators/ All data is being made publicly available as soon as it is received at https://console.cloud.google.com/storage/browser/stxfah-bucket.

KRas

A protein that plays a crucial role in cell growth and division.

KRas is a protein found within cells that acts as a molecular switch controlling cell growth. When active, it signals for cells to divide; however, mutations in KRas can cause it to remain constantly 'on,' leading to uncontrolled cell growth and cancer.

GDP

Guanosine Diphosphate

GDP is a molecule that binds to KRas, keeping it in an inactive state. When GDP is replaced with GTP, KRas becomes active and signals for cell growth.

GTP

Guanosine Triphosphate

GTP is a molecule that binds to KRas, activating it and triggering cell growth signaling. When GTP is broken down into GDP, KRas returns to its inactive state.

Protein

A large biomolecule composed of amino acids.

Proteins are essential building blocks and functional units within cells. They perform diverse roles, including catalyzing reactions, transporting molecules, and providing structural support.

Cancer

A disease characterized by uncontrolled cell growth and spread.

Cancer is a group of diseases where abnormal cells divide uncontrollably, invading surrounding tissues and potentially spreading to other parts of the body. It arises from genetic mutations that disrupt normal cell growth regulation.

Inhibitor

A substance that blocks or reduces the activity of a particular molecule.

Inhibitors are molecules designed to interfere with the function of specific targets, such as proteins involved in disease pathways. They are commonly used in drug development to treat various conditions.