In the laboratory, experimental chemists can readily tell the beginning chemical ingredients and the final products. But the actual reactions usually occur very quickly. “It’s like seeing all the actors before Hamlet,” said Sven Lidin, chairman of the Nobel selection committee, during the prize announcement webcast on Wednesday, “and all the dead bodies after, and then you wonder what happened in the middle. And actually there is some interesting action there, and this is what theoretical chemistry provides us with — the whole drama.”

But in the 1960s, when a computer filled a room, computer programs had to be crammed into small slices of memory, limiting what could be done. At the Weizmann Institute of Science in Israel, Dr. Warshel, who was then a doctoral student, and Dr. Levitt, who worked with Dr. Warshel as a computer programmer, calculated the behavior of molecules, even very large biological molecules, although that early work used Newtonian physics and not quantum effects.

Meanwhile, at Harvard, Dr. Karplus’s research group developed computer programs that simulated chemical reactions and employed the full power of quantum physics, which looks at physical reactions at the microscopic level. After completing his doctorate, Dr. Warshel joined Dr. Karplus’s laboratory as a postdoctoral researcher, and in 1972, they published a paper that combined quantum and classical physics in describing the chemical behavior of certain molecules.

Later, Dr. Warshel renewed his collaboration with Dr. Levitt, who had completed his doctorate at the University of Cambridge in England, expanding their programs to tackle enzymes, which are proteins that govern chemical reactions in living organisms. From bouncing X-rays off proteins, chemists knew the shapes of some enzymes, but less about their functions.

“It’s like seeing a watch and wondering how it actually works,” Dr. Warshel said. “So in short, what we developed is a way, which required a computer, to take the structure of a protein and then to eventually understand how exactly it does what it does.”

They found that they could not understand the behavior of the enzyme without including the effects of the surrounding molecules — water, in particular. “This was really, in my view, the conceptual breakthrough,” Dr. Warshel said. “I realized that everything you want to do with computers could be done if you make it simple enough. We wrote in a way that did not require too much memory.”

Experimental scientists were slow to accept the new work, Dr. Warshel said. “When you do something on computer, it’s very easy to dismiss it and say you made it up,” he said. He said the experimentalists were happy when the calculations agreed with the experiments, but not when Dr. Warshel claimed to be describing phenomena not seen in the experiments.