RESEARCH: ALZHEIMERS
FOLDING PROJECT #12487 PROFILE

This project explores new ways to find drugs using computer simulations. It focuses on a specific enzyme called AChE, which plays a role in memory and movement. By understanding how molecules bind to AChE, scientists can design new drugs that target this enzyme for treating diseases like Alzheimer's.

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 that breaks down acetylcholine, a neurotransmitter. This process allows for efficient communication between nerve cells and is essential for functions like muscle movement and memory. Drugs targeting AChE are used to treat Alzheimer's disease by increasing acetylcholine levels in the brain.

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AChE

Acetylcholinesterase

AChE is a common abbreviation for Acetylcholinesterase, an enzyme essential for breaking down acetylcholine in the nervous system.

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Pesticides

Substances used to kill pests.

Pesticides are chemical products designed to control unwanted organisms like insects, weeds, and rodents. They can be harmful to the environment and human health if not used responsibly.

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Nerve Agents

Substances that disrupt nerve function.

Nerve agents are highly toxic chemicals that interfere with the nervous system, causing paralysis and potentially death. They are primarily used as weapons but can also be accidental releases.

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Alzheimer's Disease

A progressive brain disorder that affects memory and cognitive function.

Alzheimer's disease is a neurodegenerative condition that gradually damages the brain, leading to memory loss, confusion, and difficulty with daily activities. It is the most common cause of dementia.

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Donepezil

A drug used to treat Alzheimer's disease.

Donepezil is a medication prescribed for Alzheimer's disease. It works by inhibiting the action of acetylcholinesterase (AChE), allowing more acetylcholine to remain active in the brain and potentially slowing cognitive decline.

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Rivastigmine

A drug used to treat Alzheimer's disease.

Rivastigmine is another medication used for Alzheimer's disease. It functions similarly to donepezil by inhibiting acetylcholinesterase (AChE), increasing acetylcholine levels in the brain.

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Virtual Screening

A method for identifying potential drug candidates.

Virtual screening is a computer-based technique used in drug discovery to rapidly screen large libraries of molecules for those that might interact with a specific target (like a disease-causing protein). This helps to narrow down the search for promising drug candidates.

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Binding Free Energy

The energy required to bind two molecules together.

Binding free energy is a measure of the strength of interaction between two molecules. In drug discovery, it helps predict how well a potential drug candidate will bind to its target.

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Alchemical Transformation

A theoretical process used in computer simulations.

Alchemical transformation is a computational technique used in drug design. It involves gradually changing the structure of a molecule within a simulation to understand how changes in its properties affect its binding affinity.