The diseases that may eventually be treated more effectively because of Jorgensen's computer programs range from dementia to diabetes. Scientists recently discovered, for example, that some medications that bind to a protein called FKBP can stimulate the growth of nerve and brain cells, which makes them excellent candidates for treating spinal cord injuries as well as Parkinson's and Alzheimer's diseases. FKBP also plays a role in transplant rejection, making it a doubly important protein to control.
Jorgensen and his co-workers have performed calculations on FKBP with a series of potential drugs, analyzing why they vary in binding strengths and suggesting ways to improve their design -- work that Jorgensen will describe on March 31 at the ACS annual meeting. The Yale chemists also have analyzed drugs that regulate the protein thrombin, which is important for controlling blood clotting.
Another application being explored in Jorgensen's laboratory is the development of improved anti-HIV drugs that counter mutant strains that are resistant to current drugs, such as AZT and the protease inhibitors. Jorgensen's calculations also have been applied to potential drugs that can regulate the natural synthesis of insulin for diabetics in a gene therapy approach involving implanted cells.
Vast Increases in Computer Speed
Vast increases in computer speed in recent years make it possible
to perform complex computations of chemical processes in minutes instead
of days, said Jorgensen, who has created a supercomputer in his Yale
laboratory by linking together 25 Pentium machines in a network. He and
his colleagues now can analyze between 50 and 100 chemical variations, or
analogs, of a leading drug each week, he said. Drug companies freq
Contact: Cynthia Atwood