Michael Levitt and Computational Biology
Levitt … shares the … prize with Martin Karplus … and Arieh Warshel … "for the development of multiscale models for complex chemical systems."
Levitt's work focuses on theoretical, computer-aided analysis of protein, DNA and RNA molecules responsible for life at its most fundamental level. Delineating the precise molecular structures of biological molecules is a necessary first step in understanding how they work and in designing drugs to alter their function. …
Levitt's early work pioneered computational structural biology, which helped to predict molecular structures, compute structural changes, refine experimental structure, model enzyme catalysis and classify protein structures. His basic research set the stage of most subsequent work in the rapidly growing field. It also led to practical methods for antibody humanization that are key for modern anticancer therapy, such as the drug Avastin.
Roger Kornberg … got an early morning phone call at home from an excited Levitt. "Michael is one of my closest friends in the world," said Kornberg, … who has known Levitt since the two studied together at Cambridge in the early 1970s. They also have co-authored many papers. … "I regard Michael as the founder of computation biology, the leading figure in the field. He is a gem of a person. You will never find a more generous or modest individual."
Levitt's early work in the late 1960s set the stage for an entirely new way to predict how proteins fold and interact. At that time, X-ray crystallography was used to ascertain the location of atoms like hydrogen, carbon and oxygen in larger molecules like proteins or DNA. Researchers then used the data to construct very large three-dimensional models out of plastic balls and metal sticks in order to better understand what the molecules looked like and how they might work.
"Molecules work because of their structure," Levitt said. "And cells worked because of where things are placed inside. The only way to interfere is to first learn their three-dimensional structure. If you wanted to change a city, but had no idea of where the buildings are, you would have no idea where to start." …
Levitt feels the computer industry deserves a large part of the credit for the work he's been able to accomplish throughout his career.
"Computers and biology go together. Biology is very complicated, and computers are such wonderful, powerful tools. And they just keep getting more and more powerful."
Proteins consist of strings of molecules called amino acids, like beads on a necklace. Unlike a necklace, however, proteins don't coil upon themselves passively but instead assume specific three-dimensional shapes governed by the interactions among the atoms of their amino acids — some of which attract each other and some of which push one another away. Laws of chemistry and physics dictate that a resting protein molecule will assume a conformation that balances these push-pull forces in a way that minimizes its energy state. These laws also affect how two or more molecules interact to carry out enzymatic interactions or other biological interactions.
"Proteins are not just good to eat, but they have specific shapes," Levitt said. "Although they consist of many thousands of atoms, they are governed by the same laws that govern the structure of bridges and houses. Everything is highly organized."
Edited excerpts from Michael Levitt Wins Nobel Prize in Chemistry
Additional information about Michael Levitt, computational biology, chemistry, molecules, and protein is available in electronic documents and on the Web.
A Novel Method for Sampling Alpha-Helical Protein Backbones; DOE Technical Report; 2001
Additional Web Pages:
Stanford’s Nobel Chemistry Prize Honors Computer Science, San Jose Mercury News
Without Test Tubes, 3 Win Nobel in Chemistry, The New York Times
The Science Behind Michael Levitt’s Nobel Prize, Stanford Report
The Levitt Lab, CSB | Computational Structural Biology, Stanford
Michael Levitt - Bio