RESEARCH: ALZHEIMERS
FOLDING PROJECT #12482 PROFILE

This project is finding new ways to design drugs that block the enzyme Acetylcholinesterase (AChE). Blocking AChE can help treat Alzheimer's disease and protect against nerve damage from pesticides. The project uses computer simulations to predict how well different molecules will bind to AChE and potentially act as new drugs.

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 in the nervous system. It breaks down the neurotransmitter acetylcholine, allowing for its recycling and enabling proper nerve signal transmission. AChE inhibitors are used in treating Alzheimer's disease by boosting acetylcholine levels.

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Alzheimer's Disease

A neurodegenerative disease characterized by memory loss and cognitive decline.

Alzheimer's disease is a progressive brain disorder that leads to memory loss, thinking difficulties, and behavioral changes. It is the most common cause of dementia, affecting millions worldwide.

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Donepezil

A drug used to treat Alzheimer's disease.

Donepezil is a medication prescribed to manage the symptoms of Alzheimer's disease. It works by inhibiting acetylcholinesterase, an enzyme that breaks down acetylcholine, thereby increasing its levels in the brain and improving cognitive function.

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Rivastigmine

A drug used to treat Alzheimer's disease.

Rivastigmine is another medication used to manage symptoms of Alzheimer's disease. It functions similarly to donepezil by inhibiting acetylcholinesterase, enhancing acetylcholine levels in the brain.

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AChE

Acetylcholinesterase

AChE stands for Acetylcholinesterase. It is an enzyme that plays a vital role in breaking down acetylcholine, a neurotransmitter involved in nerve signal transmission.

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Virtual Screening

A computational method for identifying potential drug candidates.

Virtual screening uses computer simulations to evaluate the binding affinity of thousands of molecules to a target protein, such as an enzyme. This helps researchers identify promising drug candidates that can be further investigated in laboratory experiments.