Articles by Dan Renzetti

Science

Decades later, a Yale chemist’s water simulations continue to make waves

Like many successful researchers, Jorgensen has been guided by scientific pursuits his entire life. As a kid growing up in Port Washington, a hamlet on the western side of Long Island, and later in Sherman, Connecticut, he conducted scores of experiments with his trusty A.C. Gilbert chemistry set, tromping off to the local drug store regularly to replenish his supply of potassium nitrate. In high school, at Phillips Exeter Academy in New Hampshire, he took AP Chemistry and taught himself how to write computer code in BASIC. He went on to graduate from Princeton in three years, learning the computer language FORTRAN in the basement of the Frick Lab and conducting work for his first co-authored study in the Journal of the American Chemical Society. Then it was on to Harvard for graduate school (where he worked with eventual Nobel winner EJ Corey), and to Purdue to begin his teaching and independent research career. He soon came to focus his research on the need for better simulations of systems in solution. “I realized very quickly that I wanted to study reactions in liquids and investigate the way molecules recognize each other in solution, which can lead eventually to drug design,” Jorgensen said. “In drug design you typically have an inhibitor, a small molecule that is binding to a disease-causing protein, which then disrupts the function of that protein.” To do this work, he needed computing know-how and processing muscle. So, he taught himself statistical mechanics to go with his working knowledge of programming, and he got together funding for a research computer. In the late 1970s, Purdue had two CDC 6400s (an early mainframe computer built by the Control Data Corporation) in its computer center. That meant two processors for 40,000 students and faculty, compared to today when the average laptop computer has eight processors. But times were changing. “Fortunately, I was in the right place at the right time, because by the early 1980s computer resources became more available,” Jorgensen said. “You could have your own computer in your lab, if you could find the money to buy it.” He and his research group purchased a Harris 80 — a tall cabinet computer that occupied its own room with an air conditioner and a printer. Much of the funding for it came from a 1978 grant to Jorgensen from the National Science Foundation (NSF). “NSF was essential to the early work I did, including the water models,” Jorgensen said. “NSF funded basic science research that led to many of the technologies and therapeutics we take for granted today.” Meanwhile, the older guard of scientists, who’d previously held computer modeling at arm’s length began to see the value of adapting to changing technology. “In the late 1970s you had people still trying to do paper-and-pencil theory work, but you also had the new people coming in with their computers,” Jorgensen said. “There was some difficulty in my being accepted by some of the theoretical chemists at the time, who were rather dismissive of what I was doing. I had to prove I could do something useful.”