RSS Feed Understanding the Movement of Chemicals Into and Out of Enzyme Active Sites.
Department of Chemistry at The Catholic University of America
Enzymes are primarily proteins which have an active site where chemical transformations occur. There is at least one path to the active site along which the substrate for the enzyme approaches and the resulting products leave.
The enzyme studied here is acetylcholinesterase (AChE), which deactivates the neurotransmitter acetylcholine. The enzyme works very fast, near what is expected to be its theoretical top speed. However, the path to the active site is characterized by a long, narrow, passageway, which suggests that there should be a backup of substrate waiting to get in and products waiting to get out. The scientific question is: Could there be other pathways to the active site?
There are techniques, such as x-ray crystallography, which allow researchers to take a "snapshot" of a protein to determine an average conformation for the molecule. But in order to study how the conformation of the protein changes over time, a simulation must be performed . The simulation program uses Newton's equation of motion (F=ma) to compute how the atoms must move relative to each other over very short periods of time - on the order of a few femtoseconds (10-15 sec). A fast process for a protein requires the simulation to compute hundreds of thousands of time steps (hundreds of picoseconds).
One of the unique contributions of this research is the use of a "Potential of Mean Force". This allows the simulation to sample specific pathways instead of blindly traversing all pathways until an interesting one is found.