RESEARCH: ALZHEIMERS
FOLDING PROJECT #12485 PROFILE

This project is about finding new drugs that can treat Alzheimer's disease. It uses computer simulations to test how well different molecules bind to an enzyme called acetylcholinesterase. Blocking this enzyme helps keep a brain chemical called acetylcholine active, which is important for memory and movement.

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.

---

Acetylcholinesterase

Enzyme that breaks down acetylcholine.

Acetylcholinesterase (AChE) is a crucial enzyme in the nervous system. It breaks down the neurotransmitter acetylcholine, allowing for proper nerve signal transmission and recycling of this important chemical messenger. AChE inhibitors are used to treat Alzheimer's disease by boosting acetylcholine levels in the brain.

---

AChE

Acetylcholinesterase

AChE is a shorthand for Acetylcholinesterase. It refers to the enzyme that breaks down acetylcholine in the nervous system.

---

Pesticides

Substances used to kill pests.

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

---

Nerve Agents

Chemicals that disrupt nerve function.

Nerve agents are highly toxic substances used in chemical warfare. They interfere with the nervous system, leading to paralysis and potentially death.

---

Alzheimer's Disease

A neurodegenerative disease.

Alzheimer's disease is a progressive brain disorder that causes memory loss, cognitive decline, and behavioral changes. It is the most common cause of dementia.

---

Donepezil

A drug used to treat Alzheimer's disease.

Donepezil is a medication prescribed for Alzheimer's disease. It works by inhibiting the enzyme acetylcholinesterase, which increases levels of acetylcholine in the brain.

---

Rivastigmine

A drug used to treat Alzheimer's disease.

Rivastigmine is another medication for Alzheimer's disease. It functions similarly to donepezil by inhibiting acetylcholinesterase and boosting acetylcholine levels.

---

Virtual Screening

A method for identifying potential drug candidates.

Virtual screening uses computer simulations to evaluate the interactions between molecules and target proteins. This helps researchers identify promising drug candidates before expensive and time-consuming laboratory experiments.

---

Free Energy Methods

Calculations that predict the energy changes associated with chemical reactions.

Free energy methods are used in computational chemistry to predict the stability and reactivity of molecules. They are essential for understanding drug-target interactions and designing new drugs.