By: TOP500 Team

Since phospholipase A2 (PLA2) enzymes play a role in many inflammatory diseases, it stands to reason they can usher in a new class of anti-inflammatory medication. To better understand these enzymes and help drive therapeutic drug development, researchers at the University of California, San Diego (UC San Diego) School of Medicine went to the Pittsburgh Supercomputing Center to develop 3D computer models. These visualizations show exactly how two PLA2 enzymes extract their substrates from cellular membranes.

“This is the first time experimental data and supercomputing technology have been used to visualize an enzyme interacting with a membrane,” says Edward Dennis, senior author of the study funded by the US National Institutes of Health, US National Science Foundation, and Howard Hughes Medical Institute.

“We discovered that binding the membrane triggers a conformational change in PLA2 enzymes. We also saw several important differences between the two PLA2 enzymes we studied — findings that could influence the design and development of specific drugs for each enzyme.”

The computer simulations of PLA2 enzymes developed by Dennis and his team, including first author Varnavas Mouchlis, show the specific molecular interactions between PLA2 enzymes and their substrate, arachidonic acid (an inflammatory medium commonly referred to as AA), as the enzymes suck it up from cellular membranes.

Read the full article on iSGTW.