RESEARCH: CANCER
FOLDING PROJECT #18108 PROFILE

This project uses computer simulations to study how proteins change shape. They're focusing on caspase-7, a protein important for cancer treatment. Experimental data is used to guide the simulations, making them more accurate. All data and results are publicly available.

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 at https://console.cloud.google.com/storage/browser/stxfah-bucket, 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/ All data is being made publicly available as soon as it is received at https://console.cloud.google.com/storage/browser/stxfah-bucket.

caspase-7

An enzyme involved in apoptosis (programmed cell death).

Caspase-7 is a crucial protein that plays a role in programmed cell death, known as apoptosis. Apoptosis is essential for removing damaged or unwanted cells from the body. Dysregulation of caspase-7 can contribute to cancer development and progression.

apoptosis

Programmed cell death.

Apoptosis is a natural process of cellular self-destruction that eliminates damaged or unnecessary cells. It plays a vital role in development, tissue homeostasis, and immune system function. Cancer cells often evade apoptosis, contributing to their uncontrolled growth.

hydrogen-deuterium exchange (HDX)

Hydrogen-Deuterium Exchange

HDX is a technique used to study the structure and dynamics of proteins. It involves measuring the exchange rate of hydrogen atoms in a protein with deuterium atoms from a heavy water solution. The rate of exchange provides information about the accessibility and flexibility of different regions of the protein.

apo

Without a ligand or substrate bound.

In biochemistry, 'apo' refers to a protein that lacks its bound molecule or ligand. For example, an apoprotein is a protein without its attached prosthetic group.

holo

With a ligand or substrate bound.

'Holo' refers to a protein that has its bound molecule or ligand attached. A holoenzyme is an enzyme with its cofactor bound.