Web Exclusives: Chemistry
The Legacy of John Pople
When quantum mechanics burst onto the scene in the early 1900s, physicists rejoiced. Using mathematical descriptions, they could finally pry into the secrets of how electrons interact with protons and neutrons in atoms to form the vast range of matter that makes up the universe.
Chemists, however, had to postpone their celebration. The math to understand the details of atomic bonds—the heart of chemistry—was still too complicated to tackle for most molecules.
Sixty years later, an English mathematician and chemist named John Pople came up with a Nobel Prize-winning solution using computation.
Pople had already built a solid reputation in several chemistry subjects. Then he decided to turn his attention to quantum mechanics.
At the time, chemists didn't have the computing power to translate physical laws into a prediction of how molecules behave in a chemical reaction. So Pople's first step was to use approximate or "semi-empirical" methods. This let him mix experimental data with pure theory to lessen the computer's burden and build workable models that are still used today.
The next major step happened in 1970. Pople took advantage of slowly maturing computer technology to create a program that could do what scientists call ab initio ("from the beginning" or "first principles") calculations: extrapolating molecular behavior purely from the fundamental laws of physics.
Pople's program was remarkably efficient and had the potential to deliver highly accurate answers to complex chemical questions. He called it Gaussian 70, and it played a part in earning him a 1998 Nobel Prize in chemistry.
Bringing Quantum Chemistry to the Masses
Chemistry labs around the world seized upon the possibilities of Pople's software. Quantum chemists used Gaussian to test new methods, while experimental chemists used it to learn about the structures and properties of molecules.
Above all, Gaussian "transformed quantum mechanics from an abstract theory into a practical tool to solve practical problems," says Jiali Gao, a theoretical and computational chemist at the University of Minnesota. "It brought quantum chemistry into the lab. Suddenly experimentalists with little or no theoretical training could do quantum calculations."
That was partly a testament to Gaussian's user-friendly design—a reason the software continues to be widely used today.
"There are many quantum mechanics packages today, but no other can compare with Gaussian" on user-friendliness, says Gao. "Anyone can use Gaussian to calculate the structure and properties of molecules very easily. It's an integral tool now to supplement and explain experimental observations."
Along with similar computer programs, adds University of Florida chemist Kennie Merz, "Gaussian has really been a foundation in computational chemistry by increasing our understanding of basic molecular structure."
Gaussian's success can also be measured by the number of other computational chemists who helped develop and expand it over the years. The original program had five coauthors, while the current edition has more than 70.
The Next Frontier: Biology
Pople's work addressed small to medium-sized molecules and chemical systems. Now researchers are looking to expand on it to address large molecules and entire biological systems.
Gao, for instance, wants to use quantum calculations to more accurately understand complex systems such as drug interactions and protein dynamics. Computational biologists currently use equations called force fields, which treat molecules like balls (atoms) connected by springs (bonds), to study such questions. Force fields can track thousands and even millions of molecules.
Gao is developing a computer software program based directly on Pople's earlier work with semi-empirical theory that replaces force fields with quantum mechanics. Although the calculations would take longer, he says the results would be more precise. The goal, he says, is to "bring chemical accuracy" to drug design and many other biological applications, including modeling proteins, chemical reactions and photosynthesis.
In the end, all this work "traces back to John Pople's contributions," says fellow chemist Merz. "He laid the foundation for modern semi-empirical quantum theory, and everyone has been building on it since."