RESEARCH: CANCER
FOLDING PROJECT #18124 PROFILE

Scientists are studying KRAS, a protein that can cause cancer when it's malfunctioning. This project uses computer simulations to understand how drugs work against mutated KRAS. Researchers hope this will lead to better cancer treatments and all data is available publicly.

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 role in cell growth and division.

KRas is a protein that acts like a switch, controlling whether cells grow and divide. When it's 'on', cells multiply rapidly. In many cancers, KRas becomes stuck in the 'on' position, leading to uncontrolled cell growth.

GDP

Guanosine Diphosphate

GDP is a molecule that binds to KRas protein, turning it 'off' and stopping cell growth. When GDP is bound to KRas, the protein can't signal for cell division.

GTP

Guanosine Triphosphate

GTP is a molecule that binds to KRas protein, turning it 'on' and allowing cell growth. When GTP is bound to KRas, the protein signals for cell division.

Inhibitor

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

Inhibitors are molecules designed to stop KRas from functioning properly. They are being developed as potential cancer drugs because they can prevent uncontrolled cell growth.

Protein

A large biological molecule made up of amino acids.

Proteins are the workhorses of cells. They carry out a vast array of functions, including building and repairing tissues, catalyzing chemical reactions, and transporting molecules.

Cancer

A disease characterized by uncontrolled cell growth.

Cancer is a group of diseases where cells divide and grow uncontrollably. This can lead to the formation of tumors that invade surrounding tissues.