RESEARCH: CANCER
FOLDING PROJECT #16499 PROFILE

This project explores new ways to find drug targets for cancer. Researchers are using computer simulations to 'boost' the exploration of protein shapes, hoping to discover unique conformations in proteins like MET kinase that could be targeted by new drugs. This approach aims to overcome limitations of traditional simulation methods and potentially lead to more effective cancer treatments.

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

In drug discovery, particularly that of cancer, maximizing state exploration is a useful novel strategy – providing new protein states and conformations to point drug design methods at increases the likelihood that a potential binder and inhibitor may be found.

However, in many cases a new state that is "useful for design" (ie.

ones distinct enough to be worth targeting to identify novel drugs) require a lot of sampling or simulation.

Sometimes, even exascale computers like Folding@home are not enough! Adaptive methods are very powerful here, but have the drawback of requiring system knowledge, or having to guess which protein features are worth adaptively exploring on, which may not always turn out to be true.

Another promising strategy, explored in these projects, is to "Accelerate" the simulations.

By broadly applying "boosters" to the simulation, we effectively "flatten" the energy landscape of a protein's conformations, allowing the protein to visit states more easily than it normally would.

Alongside the ability to discover new states that we can seed simulations of, just like adaptive sampling simulations, these boosters have specific technical and physiclal properties that allow us to infer something about a new state's "accessibility" (ie where it exists on the landscape). In projects 16497–16499 we test three such boosters to accelerate our simulations to identify how well boosted simulations work for our purposes.

Here we apply it to the protein MET kinase, a protein drug target in many cancers such as non-small-cell lung carcinoma.

MET kinase is targeted by the drug crizotinib but often evolves resistance against the drug, rendering it ineffective.

With our boosted simulations we hope to observe never before seen states of MET!.

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drug discovery

The process of identifying and developing new medications.

Drug discovery is the scientific process used to find and develop new medicines. It involves many steps, from identifying a disease target to testing and manufacturing the final drug product.

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cancer

A group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body.

Cancer is a group of diseases caused by uncontrolled cell growth. These cells can divide rapidly and spread to other parts of the body, damaging tissues and organs.

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protein

Large biomolecules essential for the structure and function of all living organisms.

Proteins are large molecules made up of building blocks called amino acids. They have many important functions in the body, such as building tissues, transporting molecules, and catalyzing chemical reactions.

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drug design

The process of using scientific knowledge to create new medications that target specific diseases or conditions.

Drug design is a complex process that involves understanding how drugs interact with the body. Scientists use this knowledge to design new molecules that can effectively treat diseases.

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MET kinase

A type of enzyme (kinase) involved in cell growth and signaling, often overexpressed or mutated in cancer.

MET kinase is a protein that controls cell growth and division. When it's overactive, it can contribute to the development of cancer.

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crizotinib

A targeted therapy drug used to treat certain types of non-small-cell lung cancer.

Crizotinib is a medication that blocks the activity of MET kinase. It's used to treat some types of lung cancer.

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simulations

Computer models used to imitate complex systems or processes.

Simulations are computer programs that create virtual environments to study how things work. They can be used to model anything from weather patterns to the spread of disease.