RESEARCH: CANCER
FOLDING PROJECT #18116 PROFILE

Scientists are using computer simulations to study how a protein called KRas binds to small molecules. This project aims to understand how KRas works and potentially design new drugs that target it. The data from this research is being made publicly available.

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 protein that plays a crucial role in cell growth and division. Mutations in the KRas gene can lead to uncontrolled cell growth, contributing to the development of various cancers.

G12D

Glycine to Aspartic Acid at codon 12

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

GDP

Guanosine diphosphate

GDP is a molecule that plays a vital role in cellular processes, including signal transduction and protein synthesis. It acts as a precursor to GTP (guanosine triphosphate), which is involved in many energy-dependent reactions.

KRpep

KRas peptide inhibitor

KRpep is a synthetic peptide designed to inhibit the activity of KRas protein. Peptides are short chains of amino acids, and they can be used as therapeutic agents by targeting specific proteins involved in disease processes.

Binding Pose

The specific 3D arrangement of a molecule (ligand) when bound to another molecule (protein).

Binding pose describes how a molecule, such as a drug or peptide, fits into the active site of a protein target. Understanding binding poses is crucial for designing effective drugs as it allows scientists to optimize the interaction between the drug and the target.

Simulation

A computer model that imitates the behavior of a system over time.

Simulations are used in various fields, including drug discovery, to study complex biological processes. By running simulations, researchers can explore different scenarios and gain insights into how molecules interact and influence each other.