RESEARCH: CANCER
FOLDING PROJECT #18121 PROFILE

Scientists are studying how KRas, a protein that controls cell growth, works with drugs designed to stop cancer. They're using computer simulations and making their findings public to help develop new cancer treatments. This project is led by Roivant Sciences and uses the Folding@home platform.

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. When mutated, it can contribute to the development of cancer by constantly signaling for cell growth, leading to uncontrolled proliferation.

GDP

Guanosine diphosphate

GDP is a nucleotide molecule that acts as an energy source and signaling molecule within cells. It plays a role in regulating various cellular processes, including protein synthesis and cell growth.

GTP

Guanosine triphosphate

GTP is a nucleotide molecule that plays a vital role in cellular energy production and signal transduction. It acts as an activating molecule for various proteins, including those involved in cell growth and division.

Inhibitors

Substances that block or reduce the activity of a specific biological target, such as an enzyme or receptor.

Inhibitors are molecules designed to interfere with the function of certain proteins or processes. They are commonly used in drug development to treat diseases by blocking harmful pathways.

Protein

A large biomolecule composed of chains of amino acids that perform a wide range of functions in living organisms.

Proteins are the workhorses of cells, carrying out essential functions such as catalyzing reactions, transporting molecules, and providing structural support. Their diverse structures and functions make them crucial for life.

Small molecule

A relatively small organic compound that can interact with biological targets, such as proteins or receptors.

Small molecules are often used in drug development due to their ability to penetrate cells and modulate biological processes. They can be designed to target specific proteins involved in disease pathways.