RESEARCH: CANCER
FOLDING PROJECT #18100 PROFILE

This project uses computer simulations to understand how a protein involved in cell death (caspase-7) changes shape when it binds to other molecules. Researchers collected experimental data on the protein's flexibility and are using AI algorithms to match these results. The goal is to design better cancer drugs by learning how this protein works at the molecular level. All data and methods will be made public.

Here we are testing what has long been the dream on F@h --- adaptive sampling algorithms guided by experimental data.

The system used is caspase-7, one of a family of important mediators of apoptosis, and hence of interest for cancer drug design.

We have collected experimental hydrogen-deuterium exchange (HDX) data (which informs on the extent of fluctuations of each region of the protein) in both apo (just protein) and holo (protein with another peptide bound) states, and are exploring adaptive sampling algorithms to reproduce the HDX data in each state separately, as well as the differences ('shielding') between them.

All data is being made publicly available, and insight into the algorithmic methodology will be published. 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/.

caspase-7

A protein involved in apoptosis (programmed cell death).

Caspase-7 is a crucial enzyme that plays a vital role in apoptosis, the process of programmed cell death. When cells are damaged or no longer needed, caspase-7 helps to break down cellular components in a controlled manner. This process is essential for normal development and tissue homeostasis. Dysregulation of caspase-7 can contribute to various diseases, including cancer.

apoptosis

Programmed cell death.

Apoptosis is a natural process of programmed cell death that is essential for the proper functioning of multicellular organisms. It plays a crucial role in removing damaged or unwanted cells, maintaining tissue homeostasis, and preventing the development of diseases like cancer. During apoptosis, cells undergo a series of controlled steps that lead to their dismantling and removal by other cells.

HDX

Hydrogen-Deuterium Exchange

Hydrogen-Deuterium Exchange (HDX) is a technique used to study the structure and dynamics of proteins. It involves replacing hydrogen atoms in a protein with deuterium atoms from heavy water. The rate at which these exchanges occur provides information about the accessibility and flexibility of different regions within the protein.

apo

Without a ligand bound.

In biochemistry, 'apo' refers to a protein that is not bound to any ligand or cofactor. For example, apoprotein is a protein without its attached prosthetic group.

holo

With a ligand bound.

'Holo' refers to a protein that is bound to its specific ligand or cofactor. For example, holoenzyme is an enzyme with its attached cofactor.