RESEARCH: CANCER
FOLDING PROJECT #18114 PROFILE

This project uses computer simulations to study how a special molecule called KRpep binds to a protein called KRas. KRas is involved in cancer, so understanding how molecules bind to it could lead to new drugs. The project will explore different binding positions and analyze the interactions between KRas and KRpep. Results will be publicly available online.

Note: This TLDR is a simplication and may not be 100% accurate.

18110: 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: 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.

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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 the development of cancer.

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G12D

Glycine to Aspartic acid at position 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 frequently found in various cancers and is associated with increased cancer cell growth and survival.

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GDP

Guanosine diphosphate

GDP is a molecule that acts as an energy source and signaling molecule within cells. It plays a crucial role in various cellular processes, including protein synthesis and signal transduction.

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KRpep-2d

A specific KRas peptide ligand

KRpep-2d is a synthetic peptide designed to bind to the KRas protein. It acts as a potential drug candidate for targeting and inhibiting the growth of cancer cells driven by mutated KRas.

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Binding Simulation

A computational method to predict the interactions between molecules in a system

Binding simulations use computer models to analyze how different molecules, such as drugs and proteins, interact with each other. These simulations help researchers understand how drugs bind to their targets and can be used to design more effective therapies.

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Binding Pose

The specific orientation and position of a molecule when bound to its target

Binding pose describes how a molecule, like a drug, fits into the active site of a protein target. Understanding the binding pose is crucial for designing drugs that effectively interact with their intended targets.

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Folding@home

A distributed computing project for simulating protein folding and other biomolecular processes.

Folding@home harnesses the power of volunteer computers to perform complex simulations of protein folding. This massive computational effort accelerates research into diseases like Alzheimer's and cancer.

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Roivant Sciences

A biotechnology company focused on developing new therapies for a range of diseases.

Roivant Sciences is a biopharmaceutical company that utilizes innovative approaches to develop and commercialize treatments for various conditions. They are known for their focus on rapidly translating research discoveries into clinical applications.