RESEARCH: CANCER
FOLDING PROJECT #16491 PROFILE

Scientists are studying how RIPK2, a protein involved in cancer, interacts with other proteins. They're using computer simulations to understand how three existing drugs block this interaction. This could lead to better cancer treatments by improving these drugs.

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

Kinases are a major target for a variety of cancer therapies, but their mechanism of action is relatively unknown at a detailed atomic level, preventing us from understanding and optimizing known inhibitors.

One example is the Serine/Threonine Kinase RIPK2.

RIPK2 inhibition is useful for cancer targeting as it prevents RIPK2 from binding a protein partner named XIAP.

In fact, there are already 3 known inhibitors that bind to RIPK2 and prevent RIPK2-XIAP binding! However, it remains difficult to optimize these ligands for clinical purposes because we do not understand how any of these three inhibitors actually act on RIPK2 to prevent XIAP binding behavior.

These four projects are simulating RIPK2 by itself and bound to each of the three inhibitors, with the hope that this will reveal a more detailed mechanism of how each inhibitor works to prevent XIAP binding.

As a bonus, this will help reveal how RIPK2 *binds* XIAP (also unknown)! In this set of projects we are studying the following systems: 16466 – RIPK2 16467 – RIPK2:CSLP43 inhibitor-bound complex 16468 – RIPK2:CSLP48 inhibitor-bound complex 16469 – RIPK2:GSK583 inhibitor-bound complex 16470 – RIPK2:WEHI-345 inhibitor-bound complex 16471 – RIPK2:BI inhibitor-bound complex 16488 – RIPK2:BI inhibitor-bound complex (alt configuration) 16489 – RIPK2:BI inhibitor-bound complex (alt configuration 2) 16490 – RIPK2:NVS inhibitor-bound complex 16491 – RIPK2 apo from the GSK bound structure 16492 – RIPK2 apo fro the BI bound structure.

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Kinases

Enzymes that transfer phosphate groups.

Kinases are a type of enzyme that play a crucial role in cellular signaling pathways. They add phosphate groups to other molecules, which can activate or deactivate those molecules. Kinases are often involved in processes such as cell growth, differentiation, and survival.

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RIPK2

Receptor-interacting protein kinase 2

RIPK2 is a protein involved in cellular signaling pathways that regulate inflammation and cell death. It plays a role in the immune system's response to pathogens and has been implicated in the development of certain cancers.

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XIAP

X-linked inhibitor of apoptosis protein

XIAP is a protein that inhibits programmed cell death (apoptosis). It plays a role in the survival of cancer cells and has been targeted by some cancer therapies.

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Inhibitors

Substances that block or reduce the activity of a target molecule.

Inhibitors are compounds that can bind to and interfere with the function of other molecules, such as proteins or enzymes. They are often used in drug development to target specific biological processes.

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Ligands

Molecules that bind to a specific receptor or target site.

Ligands are molecules that can interact with other molecules, such as receptors, enzymes, or DNA. They play a role in many biological processes, including signaling, metabolism, and drug action.

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CSLP43

Cellular Senescence-Linked Protein 43

CSLP43 is a protein that has been implicated in the development of cancer. It plays a role in cell signaling and proliferation.

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GSK583

GlaxoSmithKline's compound 583

GSK583 is an experimental drug that has been shown to inhibit the growth of certain cancer cells.

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WEHI-345

Walter and Eliza Hall Institute compound 345

WEHI-345 is a drug that has been shown to inhibit the growth of certain cancer cells.

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BI

Bristol Myers Squibb compound

BI is a drug that has been shown to inhibit the growth of certain cancer cells.

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NVS

Novartis compound

NVS is a drug that has been shown to inhibit the growth of certain cancer cells.