Nobel Prize in Chemistry awarded for foundations of computational chemistry
The Nobel Prize in Chemistry has been awarded to Martin Karplus, Michael Levitt, and Arieh Warshel for the development of multi-scale computer models of chemical reactions. Such computational chemical models are now the foundation for protein, enzyme, and pharmaceutical research, and combine a classical description of the motion and structure of large molecules with a quantum description of the regions within the molecule where a reaction takes place.
A chemical reaction transforms one set of chemicals into another. How reactions occur can be described with great precision using quantum mechanics. However, the problem is that the equations of quantum mechanics cannot be solved exactly, even for simple reactions such as the rusting of iron in water. Some form of approximation is always required.
Because of their tiny weight, electrons move much more rapidly during a reaction than can the whole atoms of molecules. As a result, chemistry is mostly the study of the motions of electrons within and between the molecules involved in a reaction. One stage of approximation is to hold the atoms fixed while the electrons redistribute. However, describing the redistribution of the electrons is so complex that a quantum mechanical treatment is still impractical.
The theoretical methods developed by Karplus, Levitt, and Warshel circumvented this problem by combining classical and quantum descriptions of molecules undergoing chemical reactions. To understand this, it is helpful to think about organic chemistry.
An enzyme, for example, is a large protein that causes the reaction of other chemicals to proceed more quickly. Enzymes range in size from hundreds to thousands of atoms, but the portion of an enzyme that is active during a catalytic reaction usually involves only a handful of atoms in particular regions of the enzyme's molecular structure.
The key parts of a lyzozyme enzyme are circled - only these atoms require quantum mechanical description (Photo: Nobelprize.com)
The new Laureates realized that only these atoms had to be described in terms of quantum mechanics to predict the action of an enzyme. The vast majority of the atomic positions and electrons of the enzyme remained largely unaffected, and what influence they had on the catalytic process, such as the energy required to bend molecular bonds, could be described using classical mechanics.
In the early 1970s, Karplus developed computer programs that used quantum mechanics to simulate simple chemical reactions. However, reactions involving larger molecules were too difficult even for today's supercomputers.
At about the same time, Levitt and Warshal, a pair of PhD students at the Weizmann Institute in Israel, developed a program based on classical descriptions of chemical structure. Though this program was very accurate in describing the shape of large molecules, it was blind to the quantum mechanisms that drive chemical reactions.
When Warshal received his PhD in 1970, he joined Karplus' lab at Harvard as a postdoctoral researcher, bringing with him his classical molecular modeling program. They decided to tackle the problem of modeling the reaction of retinal to light, a reaction that is partially responsible for human sight by combining a classical description for the outlines of the process with a quantum description of the key phenomena. By 1972 they had succeeded in the retinal project. Following additional refinements of the model by Levitt and Warshal, the first modern computational chemistry program was born.
Source: Nobel Foundation