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NERSC User Martin Karplus Wins Nobel Prize in Chemistry

October 9, 2013

Contact: Linda Vu, +1 510 495 2402, [email protected]

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Martin Karplus

On Wednesday, the Nobel Prize in Chemistry was awarded to three scientists for pioneering methods in computational chemistry that have brought a deeper understanding of complex chemical structure and reactions in biochemical systems. These methods can precisely calculate how very complex molecules work and even predict the outcomes of very complex chemical reactions.

One of the laureates—Martin Karplus of Harvard University—has been using supercomputers at the Department of Energy’s National Energy Research Scientific Computing Center (NERSC) since 1998. The other laureates were Michael Levitt of Stanford University and Arieh Warshel of the University of Southern California. 

According to the Royal Swedish Academy, these accomplishments have opened up an important collaboration between theory and experiment that has made many otherwise unsolvable problems solvable. 

“Today the computer is just as important a tool for chemists as the test tube. Simulations are so realistic that they predict the outcome of traditional experiments,” writes the Royal Academy in its announcement of the winners.

Supercomputers and Modern Chemistry

Long gone are the days when chemists used plastic balls and sticks to create models of molecules. Today, modeling is carried out on computers, and Karplus’ work helped lay the foundation for the powerful programs that are used to understand and predict chemical processes. These models are crucial for most of the advances made in chemistry today.

Because chemical reactions happen at lightning speed, it is impossible to observe every step in a chemical process. To understand the mechanics of a reaction, chemists build computer models of these events to study them in detail. The models also allow researchers to look at these reactions at different scales, from electrons and nuclei at sub-atomic scale to large molecules.

Karplus, Levitt and Warshel, revolutionized the field of computational chemistry by making Newton’s classical physics work side-by-side with fundamentally different quantum physics. Previously, researchers could only model one or the other. Classical physics models were ideal for modeling large molecules, but they couldn’t capture chemical reactions. For that purpose, researchers instead had to use quantum physics. But these calculations required so much computing power that researchers could only simulate small molecules.

By combining the best from both physics worlds, researchers can now run simulations to understand complex processes like how drugs couple to its target proteins in the body. For example, quantum theoretical calculations show how atoms in the target protein interact with the drug. Meanwhile, less computationally demanding classical physics is used to simulate the rest of the large protein.

Karplus and NERSC

Karplus began computing at NERSC in 1998, with an award from Department of Energy’s Grand Challenges competition. The Grand Challenges applications addressed computation-intensive fundamental problems in science and engineering, whose solution could be advanced by applying high performance computing and communications technologies and resources.

At the time, Karplus and his colleague, Paul Bash who was at Northwestern University, were looking to understand chemical mechanisms in enzyme catalysis, which they couldn’t investigate experimentally. So they ran computer simulations at NERSC to gain a complete understanding of the relationship between biomolecular dynamics, structure and function.

One of the enzymes they looked at was a class called beta-lactamases. Researchers knew that these enzymes were responsible for the increasing resistance of bacteria to antibiotics, but the precise chemical resistance mechanisms were unknown. So Karplus and Bash ran simulations on NERSC supercomputers to investigate this mechanism at an atomic-level of detail.

In his 15 years as a NERSC investigator, Karplus and his research group have explored everything from how the molecule ATP synthase acts as a motor that fuels cells, to how myosin, the molecular engine behind muscles, operates. Today, Karplus' group is tackling the science behind molecular machines, which may someday power man-made systems, for example by converting sunlight into biofuels; working as tiny “molecular motors” capable of performing chemical analyses or other tests for “lab-on-chip” devices; or even "manufacturing" nanodevices.

Here’s a sampling of his work at NERSC over the last 15 years:

1998: Protein Dynamics and Biocatalysis

2000: Theoretical Study on Catalysis by Protein Enzymes and Ribozyme

2001: Theoretical Study on Catalysis by Protein Enzymes, Ribosome and Molecular Motors

2002: QM/MM Studies of the Triosephosphate Isomerase-Catalyzed Reaction

2005: Protein Dynamics on the Supercomputer Big Screen

2010: Discovering How Muscles Really Work


About Computing Sciences at Berkeley Lab

High performance computing plays a critical role in scientific discovery, and researchers increasingly rely on advances in computer science, mathematics, computational science, data science, and large-scale computing and networking to increase our understanding of ourselves, our planet, and our universe. Berkeley Lab’s Computing Sciences Area researches, develops, and deploys new foundations, tools, and technologies to meet these needs and to advance research across a broad range of scientific disciplines.

Founded in 1931 on the belief that the biggest scientific challenges are best addressed by teams, Lawrence Berkeley National Laboratory and its scientists have been recognized with 13 Nobel Prizes. Today, Berkeley Lab researchers develop sustainable energy and environmental solutions, create useful new materials, advance the frontiers of computing, and probe the mysteries of life, matter, and the universe. Scientists from around the world rely on the Lab’s facilities for their own discovery science. Berkeley Lab is a multiprogram national laboratory, managed by the University of California for the U.S. Department of Energy’s Office of Science.

DOE’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit energy.gov/science.