RESEARCH: CANCER
FOLDING PROJECT #18039 PROFILE

Scientists are using supercomputers to study how a protein called KRas works in cancer cells. KRas is like a switch that controls cell growth, and when it's broken, cancer can develop. This project aims to understand how drugs designed to block KRas work and could lead to new treatments for cancer.

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

Kirsten rat sarcoma viral oncogene homolog

KRas is a protein that plays a crucial role in cell growth and division. Mutations in the KRas gene are found in many types of cancer, leading to uncontrolled cell proliferation. Scientists are actively researching drugs to target KRas and treat these cancers.

GDP

Guanosine diphosphate

GDP is a molecule that binds to proteins like KRas, turning them 'off' and preventing cell growth. When GDP is replaced by GTP, the protein becomes active.

GTP

Guanosine triphosphate

GTP is a molecule that binds to proteins like KRas, turning them 'on' and stimulating cell growth. When GTP is converted back to GDP, the protein becomes inactive.

Inhibitors

Substances that block the activity of a specific protein or enzyme.

Inhibitors are molecules designed to prevent the action of KRas. By blocking KRas, researchers aim to stop cancer cell growth and spread.

Drug Design

The process of creating new medications.

Drug design involves identifying and developing molecules that can treat diseases. Researchers use various techniques to optimize drug candidates for efficacy, safety, and delivery.

Folding@home

A distributed computing project that harnesses the power of volunteers' computers to simulate protein folding and other biological processes.

Folding@home uses volunteer computing to perform complex simulations of proteins. This helps researchers understand how proteins fold and function, which is essential for drug discovery and other areas of biology.