RESEARCH: CANCER
FOLDING PROJECT #18111 PROFILE

Scientists are using computer simulations to study how a protein called KRas interacts with small molecules. They hope this will lead to new drugs that target KRas, which is involved in many cancers. The project is led by Roivant Sciences and data is 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 various cancers.

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G12D

Glycine to Aspartic Acid substitution at position 12

G12D is a specific type of mutation in the KRas gene. It involves replacing the amino acid glycine with aspartic acid at position 12 within the protein sequence. This mutation is commonly found in cancers and contributes to uncontrolled cell growth.

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GDP

Guanosine diphosphate

GDP is a molecule that plays a crucial role in cellular signaling pathways. It acts as a binding partner for proteins involved in regulating cell growth, division, and other essential processes.

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KRpep

KRas peptide inhibitor

KRpep refers to a synthetic peptide designed to bind and inhibit the activity of the KRas protein. It is being investigated as a potential therapeutic agent for cancers driven by KRas mutations.

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Binding Simulation

A computer-based method for predicting how molecules interact with each other

Binding simulations are used to understand the interactions between drugs and their target proteins. By simulating these interactions, researchers can identify potential drug candidates that bind effectively to their targets.

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Peptide Ligand

A small chain of amino acids that can bind to a protein target

Peptide ligands are short chains of amino acids that can act as drug candidates. They can bind specifically to proteins, modulating their activity and potentially treating diseases.

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Binding Pocket

A specific region on a protein where ligands bind

Binding pockets are regions on proteins that are specifically shaped to accommodate and interact with ligands, such as drugs or other molecules.

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Roivant Sciences

A biopharmaceutical company focused on developing and commercializing innovative therapies

Roivant Sciences is a pharmaceutical company dedicated to advancing treatments for various diseases. They utilize cutting-edge technologies and scientific expertise to develop new drugs and therapies.