Nobel prizewinners: Chemistry


The first in a three-part series looking at the 2013 laureates and their achievements.  By James Mitchell Crow.


Martin Karplus

Conjure up a chemist in your mind’s eye and you no doubt see a person in a white lab coat, working at a bench or fume hood, carefully tending glass flasks filled with vigorously bubbling liquids.

The winners of the 2013 Nobel Prize for Chemistry are not those kinds of chemists. They don’t even wear lab coats. These guys spend their working days at computers, simulating reactions inside virtual test tubes. Their approach has shone a light on exactly how atoms move around during the chemical reactions that underpin life, something that could never have been discovered by lab chemists alone. Their “computational chemistry” has provided an indispensable tool for today’s drug designers.

Arieh Warshel

The challenge with trying to understand any chemical reaction – for instance how plants synthesise glucose – is that it happens so quickly. The lab chemist can measure how the plant sucks in water and carbon dioxide and releases glucose and oxygen. They can observe that enzymes catalyse the process, chaperoning the reactants to keep them on the straight and narrow. But the precise movement of the atoms as they undergo the chemical reactions are impossible to observe or measure. They happen on the unfathomably minute time scale of femtoseconds (10-15 seconds).

But like sports cameras in slow motion replay, computer simulations can slow down chemical reactions to analyse the action. The Nobel winners – Martin Karplus of Harvard University and the University of Strasbourg; Michael Levitt of Stanford University; and Arieh Warshel of the University of Southern California – can stop time altogether to get a better look.

Michael Levitt

This kind of virtual chemistry was pioneered in the 1960s. Theoreticians Walter Kohn and John Pople – who shared the 1998 chemistry Nobel – used computers to simulate simple chemical reactions by solving quantum mechanics equations to map the movement of electrons, the negatively charged particles that bind atoms together into molecules and which get shuffled to make and break bonds. Kohn and Pople brought computation to chemistry. Karplus, Levitt and Warshel took it a giant leap further to biology. The difficulty was that chemistry inside living organisms invariably involves proteins. These molecular giants boast 100,000 electrons or more, far too many for a computer to simulate.

“The contribution of Karplus, Levitt and Warshel was to break the problem up into two pieces,” explains Leo Radom, a University of Sydney computational chemist who once worked with Pople. The small part of the protein directly involved in bond breaking and making had to be simulated in quantum mechanical detail, but the rest of the molecule could be sketched out much more roughly, using simple classical physics that effectively treats peripheral atoms as tiny balls on springs. This approach takes a fraction of the computer power that quantum mechanics requires, allowing large proteins to be studied, explains Radom.

The concept might sound simple enough. In fact, the laureates spent most of the 1970s getting the two parts of the calculation to fit together smoothly. Human health has been a direct beneficiary of the work. The first big problem that Levitt and Warshel tackled was to show why immune system proteins called lysozymes are so efficient at breaking down the cell walls of bacteria. Today, legions of computational chemists employed by pharmaceutical companies use the laureates’ two-step approach to help design drugs to target proteins associated with disease.

Thanks to the Nobel Prize winners, we now have a way better to understand reactions. Even the most avowed experimentalists must sometimes step away from their bubbling flasks, throw off their lab coats and pull out some virtual test tubes.

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