Supercomputing-based dimeric analog approach for drug optimization

To explore novel and rational ways of developing drugs, we have been using supercomputing-based docking as a way of uncovering properties and events in ligand-receptor complexation that are otherwise impossible to observe. After devising a "lifelike" docking program that could be applied to proteins with known 3D structure, we discovered that the Alzheimer drug THA bound not just to acetylcholinesterase's catalytic center but also to a peripheral site. This site was elusive to experimentalists but is believed to facilitate substrate binding. Accordingly, we followed a supercomputing-based dimeric analog approach for drug optimization, which culminated in a superior acetylcholinesterase inhibitor. We describe herein the essence of our approach and its implications regarding the utilization of super-computing in biomedical research.