RESEARCH: ALZHEIMERS
FOLDING PROJECT #12489 PROFILE

The project is about finding new drugs that block a brain enzyme called acetylcholinesterase (AChE). AChE breaks down a chemical messenger in the brain, so blocking it can help treat diseases like Alzheimer's. The project uses computer simulations to test different molecules and see how well they bind to AChE.

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

Acetylcholinesterase (AChE) is an enzyme that breaks down the neurotransmitter acetylcholine so it can be recycled.

AChE is essential to the nervous system, and is the target of pesticides and nerve agents.

It is also a therapeutic target in Alzheimer's disease: drugs like donepezil and rivastigmine bind to the active site of AChE and block the degradation of acetylcholine, boosting its neurotransmitter activity in cholinergic neurons needed for movement and memory. This simulation project is aimed towards computational drug discovery of new AChE inhibitors.

More specifically, we are using the AChE system to test new ways to do virtual screening.

In recent years, free energy methods for drug design have focused on relative binding free energy calculations, in which an alchemical transformation is used to probe the effects of changing substituents on a preserved molecular scaffold.

As deep machine learning enables new approaches to finding novel chemical scaffolds, however, there has been renewed interest in virtual screening through absolute binding free energy calculations, in which an entire molecule can be decoupled from the binding site.

These projects explore this approach.

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Acetylcholinesterase

An enzyme that breaks down acetylcholine.

Acetylcholinesterase (AChE) is a crucial enzyme found in the nervous system. It breaks down acetylcholine, a neurotransmitter responsible for transmitting signals between nerve cells. This process is essential for muscle movement, memory, and other cognitive functions.

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Enzyme

A protein that catalyzes biochemical reactions.

Enzymes are biological catalysts, typically proteins, that speed up chemical reactions within living organisms. They play essential roles in various processes, including digestion, metabolism, and DNA replication.

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Neurotransmitter

A chemical messenger that transmits signals between nerve cells.

Neurotransmitters are chemicals released by neurons (nerve cells) to communicate with each other. They bind to receptors on target cells, triggering various responses such as muscle contractions, hormone secretion, or changes in mood.

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Pesticide

A substance used to kill or control pests.

Pesticides are chemicals designed to eliminate unwanted organisms such as insects, weeds, or fungi. They are widely used in agriculture to protect crops and increase yields.

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Nerve Agent

A poison that specifically affects the nervous system.

Nerve agents are highly toxic substances that disrupt the normal functioning of the nervous system. They can cause paralysis, seizures, and death.

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Alzheimer's Disease

A progressive neurodegenerative disease.

Alzheimer's disease is a chronic brain disorder that gradually destroys memory and thinking skills. It is the most common cause of dementia, affecting millions worldwide.

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Drug Discovery

The process of identifying and developing new drugs.

Drug discovery is a complex multi-step process that involves identifying promising drug candidates, testing their efficacy and safety, and ultimately bringing them to market.

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Virtual Screening

A computer-based method for screening large databases of molecules.

Virtual screening uses computational models to predict the binding affinity of molecules to a target protein. It is a powerful tool for accelerating drug discovery by identifying potential candidates.

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Binding Free Energy

The energy change associated with the binding of a molecule to a target.

Binding free energy reflects the strength of the interaction between a molecule (ligand) and its target protein. It is a key parameter in understanding drug-target interactions.