RESEARCH: CANCER
FOLDING PROJECT #18120 PROFILE

The project relates to studying the KRas protein, which is involved in cell growth and cancer. Scientists are using computer simulations to understand how drugs can block this protein's activity. This research could lead to new treatments for cancers that have a mutated KRas gene.

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 involved in signaling pathways that control cell growth. Mutations in KRas are common in many types of cancer, leading to uncontrolled cell division and tumor formation. Researchers are actively developing drugs that target KRas to treat cancer.

GDP

Guanosine Diphosphate

GDP is a molecule that binds to KRas in its inactive state, preventing cell growth signaling. When GDP is replaced by GTP, KRas becomes active.

GTP

Guanosine Triphosphate

GTP is a molecule that binds to KRas, activating it and promoting cell growth signaling. When GTP is hydrolyzed to GDP, KRas returns to its inactive state.

Inhibitor

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

Inhibitors are molecules designed to interfere with the function of specific proteins, such as KRas. They are used in drug development to treat diseases by preventing the action of harmful proteins.

Drug Design

The process of designing and developing new drugs.

Drug design is a multidisciplinary field that involves identifying drug targets, synthesizing potential compounds, and testing their efficacy and safety. It plays a crucial role in the development of new therapies for various diseases.