Arieh Warshel (born 1940): From a Kibbutz to the Nobel Prize

Introduction

Arieh Warshel is an Israeli-American computational chemist and biophysicist, a professor at the University of Southern California (USC) in Los Angeles. He is best known for helping to develop QM/MM, the idea of treating the reactive part of a large molecule with quantum mechanics and the rest with classical mechanics, and for using it to explain how enzymes work. In 2013 he shared the Nobel Prize in Chemistry with Martin Karplus and Michael Levitt. His story, from a farming community to the top of theoretical chemistry, is also one of persistence and practical creativity.

Early Life and Family

Warshel was born on 20 November 1940 in Kibbutz Sde Nahum, a collective farming community in northern Israel, then British Mandate Palestine. He grew up in the kibbutz environment, which valued practical work and community life. After his school years he served in the Israeli army, and then began his university education. He has often reflected that growing up on a kibbutz taught him hard work and independence rather than formal academic habits.

Education and Mentors

Warshel studied chemistry at the Technion, the Israel Institute of Technology in Haifa, and received his bachelor's degree in 1966. He then joined the Weizmann Institute of Science in Rehovot for graduate work, where his research supervisor was Shneior Lifson, the physical chemist who also worked with Michael Levitt. He obtained his PhD in 1969. He moved to Harvard University as a postdoctoral fellow in the laboratory of Martin Karplus from 1970. After this, he returned to the Weizmann Institute and spent time in Cambridge at the MRC Laboratory of Molecular Biology, where he again worked with Michael Levitt in the mid-1970s.

Career Timeline

Major Scientific Contributions

Warshel's contributions fall into four groups. First, the hybrid quantum-classical approach with Karplus (1972) and its application to the light-absorbing molecule retinal. Second, the simplified protein model and the lysozyme QM/MM calculation with Levitt (1975-76), which introduced multiscale modelling of enzymes. Third, the empirical valence bond method, which allows a calibrated treatment of reactions in solution and in proteins. Fourth, a long series of calculations on enzymes and biological machines, such as ATP synthase and proteins in muscle, that support the idea of electrostatic preorganisation as the main basis of catalysis. For the details of the chemistry, read the companion discovery post.

Awards, Honours and Nobel Prize

• Nobel Prize in Chemistry 2013, shared with Martin Karplus and Michael Levitt, "for the development of multiscale models for complex chemical systems".
• Membership of the US National Academy of Sciences.
• Professor of Chemistry and Biochemistry at the University of Southern California.

Personality, Struggles and Lesser-Known Facts

• A kibbutz upbringing. He grew up in a farming community, far from the traditional world of the laboratory.
• Army service. He served in the Israeli army before his university studies.
• Programming from scratch. In the early days, he and his colleagues wrote their own programs and ran them on large mainframe computers, often waiting hours for results.
• A debate about enzymes. His view that electrostatic preorganisation, not motion of the protein, is the main driver of catalysis has been discussed and challenged. He defends it with calculations and engages openly in the debate.
• Delight in simplicity. He likes models that reproduce data with as few parameters as possible.

Legacy and Influence on Modern Chemistry

QM/MM is now one of the most widely used methods in computational chemistry and biochemistry. Programs used by pharmaceutical companies and academic researchers all over the world include QM/MM capability. Warshel's work established computational modelling as a way to test mechanistic hypotheses, such as how an enzyme stabilises a transition state, and not merely a way to illustrate them. His EVB method influenced later approaches for modelling chemical reactions in condensed phases. He has trained generations of students and postdoctoral fellows at USC.

Lessons for Students

• Background is not a barrier. A boy from a kibbutz became a Nobel laureate.
• Write your own tools. Warshel's methods came from creating new programs when none existed.
• Respect experiment and theory equally. His models were always tested against measured reaction rates.
• Be ready to defend an idea. Science advances through debate, and clear calculations are the best argument.

FAQ

Where did Warshel study?

He earned his bachelor's degree at the Technion and his PhD at the Weizmann Institute, then did postdoctoral work at Harvard.

Where does he work now?

At the University of Southern California in Los Angeles.

What is EVB?

The empirical valence bond method, a way to model chemical reactions in solution and enzymes by mixing valence-bond states with calibrated parameters.

How is his prize connected to the other two laureates?

Warshel worked with Karplus at Harvard and with Levitt in Cambridge; each collaboration contributed to the multiscale idea recognised by the prize.

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