RESEARCH: ALZHEIMERS
FOLDING PROJECT #12486 PROFILE

This project develops new ways to find drugs using computer simulations. It focuses on finding molecules that block an enzyme called AChE, which is important for nerve function and targeted in Alzheimer's disease treatments.

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 an enzyme crucial for the nervous system. It breaks down the neurotransmitter acetylcholine, allowing it to be recycled and enabling communication between nerve cells. AChE inhibitors are used in treating Alzheimer's disease by boosting acetylcholine levels.

---

AChE

Acetylcholinesterase

AChE stands for Acetylcholinesterase. It is a vital enzyme in the nervous system responsible for breaking down acetylcholine, a neurotransmitter.

---

Neurotransmitter

Chemical messenger in the nervous system.

Neurotransmitters are chemicals that transmit signals between nerve cells (neurons) and other cells in the body. They play a crucial role in communication within the nervous system, influencing everything from mood and behavior to muscle movement and sensory perception.

---

Alzheimer's Disease

Progressive neurodegenerative disorder.

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

---

Donepezil

Drug used to treat Alzheimer's disease.

Donepezil is a medication prescribed to manage the symptoms of Alzheimer's disease. It belongs to a class of drugs called acetylcholinesterase inhibitors, which work by increasing the levels of acetylcholine in the brain.

---

Rivastigmine

Drug used to treat Alzheimer's disease.

Rivastigmine is another medication used to treat Alzheimer's disease. Like donepezil, it belongs to the class of acetylcholinesterase inhibitors and works by boosting acetylcholine levels in the brain.

---

Virtual Screening

Process of identifying potential drug candidates.

Virtual screening is a computer-based technique used in drug discovery to identify promising drug candidates from vast databases of chemical compounds. It involves simulating the interactions between molecules and target proteins to predict their binding affinity and potential effectiveness.

---

Binding Free Energy

Energy required to break a chemical bond.

Binding free energy is a measure of the strength of the interaction between a molecule (ligand) and its target (receptor). It quantifies the energetic cost of breaking the bonds that hold the ligand-receptor complex together.

---

Alchemical Transformation

Process of changing the chemical structure of a molecule.

Alchemical transformation is a computational method used in drug design to systematically modify the chemical structure of a molecule and study the effects on its binding affinity.