RESEARCH: CANCER
FOLDING PROJECT #18040 PROFILE

Scientists are using computer simulations to study how a protein called KRas works in cancer cells. KRas is like a switch that controls cell growth, and when it's stuck on, cancer can grow uncontrollably. The project aims to understand how drugs can block KRas and potentially treat cancer. All data and findings will be made publicly available.

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 involved in cell growth signaling and often mutated in cancer.

KRas is a protein that plays a crucial role in regulating cell growth. It acts like a switch, turning on and off cellular signals that promote division. Mutations in the KRas gene can lead to uncontrolled cell growth, contributing to the development of various cancers.

Inhibitor

A molecule that blocks or reduces the activity of another molecule, such as a protein.

An inhibitor is a substance designed to interfere with the function of a specific target molecule. In drug development, inhibitors are often used to block the activity of proteins involved in disease processes.

GDP

Guanosine diphosphate

GDP is a molecule that plays a role in cellular signaling. It binds to certain proteins, such as KRas, and can regulate their activity.

GTP

Guanosine triphosphate

GTP is a molecule that plays a role in cellular energy transfer and signaling. It binds to certain proteins, such as KRas, and can activate their function.

Mutation

A permanent change in the DNA sequence of a gene.

A mutation is a change in the genetic code that can alter protein function. Mutations can occur spontaneously or be induced by environmental factors. In cancer, mutations in genes like KRas can lead to uncontrolled cell growth.

Prognosis

The likely course or outcome of a disease.

Prognosis refers to the predicted outcome of a disease. In cancer, prognosis considers factors such as tumor stage, type, and patient characteristics to estimate the likelihood of survival and disease progression.