Delta Used to Examine Enzyme Critical to Alzheimer's Disease and Glaucoma

Michael K. Gilson, T. P. Straatsma, J. Andrew McCammon, University of Houston

Using the Intel Delta at Caltech, researchers are continuing a study of the molecular dynamics of acetylcholinesterase, a key enzyme associated with both Alzheimer's disease and glaucoma. Researchers originally used a Cray Y-MP to find a "back-door" entrance into the molecule not apparent by other methods of observation. The discovery of this "back door" has brought forth new ideas concerning the mode of action of the enzyme.

In the cover article published in the March 4, 1994 issue of Science Magazine, Gilson et al. detailed how the group was attempting to learn more about how the new 'back door' works: what opens it, how far it opens, what can and can't pass through it, what closes the 'door,' and how fast. This information will help in the study of inhibitors that can block the enzyme, which may lead to medicines that have fewer side effects than current drugs being used to treat either Alzheimer's disease or glaucoma.

Using the Delta and the EulerGROMOS molecular dynamics program, Terry Clark, Stan Wlodek, and L. Ridgway Scott have joined the original group, performing a very ambitious computer simulation of the dimeric enzyme in a large periodic box of water. Acetylcholinesterase exists as a dimer of 537 residues per subunit. The enzyme is immersed in a periodic box of water which is 91 x 97 x 160 Angstroms in volume containing 40,419 water molecules. With 131,653 dynamical atoms, this system is one of the largest molecular systems modeled to date. The simulation uses 256 processors and takes approximately 20 seconds per timestep.

Source: HPCwire, March 5, 1994

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