Official Project Description
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.