RESEARCH: CANCER
FOLDING PROJECT #18115 PROFILE

This project from Roivant Sciences uses computer simulations to study how a special peptide binds to the KRas protein. Understanding this binding could help scientists design new drugs that target KRas, which is involved in many types of cancer. The simulations are run on Folding@home and data is made public in real time.

18110/5: simulation for the complex of KRas(G12D)-GDP-KRpep-2d, with the initial structure of peptide ligand in the known binding position, exploring the binding dynamics of the complex and binding poses. 18111/6: binding simulation for the complex of KRas(G12D)-GDP-KRpep-2d, with the initial structure of peptide ligand 35A away from the protein center, exploring if the correct binding pose will be observed through the simulation. 18112-18114: binding simulation for the complex of KRas(G12D)-GDP-peptide, the binding pocket and binding pose is unknown.

We start with 100 randomly sampled initial structures, in each structure, the ligand center is 40A away from the protein center, with random direction and rotation.

The simulation is aimed to identify potential binding pocket and binding poses of the peptide.

The interactions between KRas protein and the peptide would provide insights in designing small molecules that bind with KRas. 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 in real time at https://console.cloud.google.com/storage/browser/stxfah-bucket.

KRas

Kirsten rat sarcoma viral oncogene homolog

KRas is a gene that provides instructions for making a protein involved in cell growth and division. Mutations in the KRas gene can lead to uncontrolled cell growth, contributing to cancer development.

G12D

Glycine to Aspartic Acid substitution at position 12

G12D is a specific mutation in the KRas gene where the glycine amino acid at position 12 is replaced by aspartic acid. This mutation is commonly found in various cancers and promotes uncontrolled cell growth.

GDP

Guanosine diphosphate

GDP is a nucleotide molecule that plays a role in cellular signaling and energy transfer. It is often involved in protein function regulation.

KRpep-2d

KRas peptide ligand 2D

KRpep-2d is a synthetic peptide designed to bind to the KRas protein. It is used in research to study KRas function and develop potential cancer treatments.

Binding Simulation

A computer-based model that predicts the interaction between two molecules (e.g., a drug and its target protein).

Binding simulations are used to understand how molecules interact at a molecular level. They help researchers design new drugs by predicting their binding affinity and potential effects.