RESEARCH: CANCER
FOLDING PROJECT #18102 PROFILE

Scientists are studying KRas, a protein that helps control cell growth and is often mutated in cancer. The project uses computer simulations to understand how drugs work against KRas and develop new treatments. All data will be shared 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, 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/.

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 switched on, it tells cells to multiply. In many cancers, KRas becomes mutated and stays stuck in the 'on' position, causing uncontrolled cell growth.

GDP

Guanosine diphosphate

GDP is a molecule that binds to KRas when it's in its 'off' state, preventing cell growth and division.

GTP

Guanosine triphosphate

GTP is a molecule that binds to KRas when it's in its 'on' state, signaling cell growth and division.

Inhibitors

Substances that block the activity of a target molecule.

Inhibitors are molecules designed to prevent KRas from functioning properly, potentially slowing or stopping cancer growth.

Drug Design

The process of discovering and developing new medications.

Drug design involves identifying molecules that can interact with specific targets like KRas to treat diseases.

Protein Folding

The process by which a protein assumes its three-dimensional shape.

Protein folding is essential for proteins to function correctly. Studying how proteins fold can help us understand diseases and develop new treatments.