RESEARCH: CANCER
FOLDING PROJECT #17639 PROFILE

Researchers are studying how RIPK2, a protein important in cancer, interacts with other proteins. They're using computer models to see how three known inhibitors work to block this interaction. This could lead to better cancer drugs.

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 16493 – RIPK2 apo from a Gefitinib bound structure 16494 – RIPK2 apo from a Novartis-produced inhibitor 16495 – RIPK2:Gefitinib complex 16496 – RIPK2:Novartis inhibitor structure 17637 – RIPK2:RIPK2 dimer 17638 – RIPK2:RIPK2:XIAP trimer 17639 – RIPK2:RIPK2 XIAP:XIAP tetramer (1.2 Million atoms!).

Kinases

Enzymes that catalyze the transfer of phosphate groups.

Kinases are a crucial type of enzyme found in cells. They play a vital role in many biological processes by adding phosphate groups to other molecules, which can activate or deactivate them. This process is essential for cell signaling, growth, and division.

RIPK2

Receptor-interacting protein kinase 2

RIPK2 is a type of protein kinase involved in the immune system's response to infections. It plays a key role in triggering inflammatory pathways when cells detect harmful invaders like bacteria or viruses. Understanding RIPK2's function is important for developing treatments for autoimmune diseases and infections.

Inhibitors

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

Inhibitors are molecules designed to prevent other molecules from working properly. They are widely used in medicine as drugs to treat various diseases by blocking the action of harmful enzymes or proteins.

XIAP

X-linked inhibitor of apoptosis protein

XIAP is a protein that prevents cell death (apoptosis). It plays a role in regulating the immune system and protecting cells from damage. Some cancers exploit XIAP's activity to survive and resist treatment.

Ligands

Molecules that bind to specific targets, such as proteins or receptors.

Ligands are molecules that can attach to other molecules like proteins. This binding can activate or block the target molecule's function. Ligands are important in many biological processes and are widely used in drug development.

Complex

A group of two or more molecules bound together.

A complex is formed when multiple molecules interact and bind to each other. These complexes are important in many biological processes, such as enzyme function, DNA replication, and signal transduction.