Martin Karplus

Martin Karplus
Born	Martin Karplus 15 3, 1930
Birthplace	Vienna, Austria
Died	Template:Death date and age Cambridge, Massachusetts, U.S.
Nationality	Austrian, American
Occupation	Theoretical chemist, academic
Title	Theodore William Richards Professor of Chemistry, Emeritus
Employer	Harvard University, University of Strasbourg
Known for	Development of multiscale models for complex chemical systems; Karplus equation
Education	Ph.D., California Institute of Technology (1954)
Awards	Nobel Prize in Chemistry (2013)
Website	[http://mir.harvard.edu/group/karplus/pub.html Official site]

Martin Karplus (March 15, 1930 – December 28, 2024) was an Austrian-born American theoretical chemist whose work fundamentally transformed the understanding of molecular systems through computational modeling. Born in Vienna, he fled Nazi-occupied Austria as a child and eventually settled in the United States, where he built a career that spanned more than six decades at the forefront of theoretical and computational chemistry. As the Theodore William Richards Professor of Chemistry, Emeritus, at Harvard University, and as director of the Biophysical Chemistry Laboratory at the University of Strasbourg, Karplus developed methods that enabled scientists to use computers to simulate and predict the behavior of complex chemical and biological systems. In 2013, he was awarded the Nobel Prize in Chemistry, together with Michael Levitt and Arieh Warshel, "for the development of multiscale models for complex chemical systems." His contributions, including the widely used Karplus equation relating nuclear magnetic resonance coupling constants to molecular geometry, had a lasting influence on chemistry, biochemistry, and pharmacology. Karplus mentored hundreds of scientists over his career and was also an accomplished photographer.

Early Life

Martin Karplus was born on March 15, 1930, in Vienna, Austria, into a Jewish family. His early childhood coincided with one of the most turbulent periods in European history. Following the Anschluss — Nazi Germany's annexation of Austria in 1938 — conditions for Jewish families in Vienna became increasingly dangerous. The Karplus family was forced to flee their homeland, eventually emigrating to the United States to escape persecution.

The experience of displacement and the journey from wartime Europe to the United States shaped Karplus's formative years. He grew up in the United States and developed an early interest in the natural sciences. According to a 2017 retrospective in the Harvard Gazette, Karplus reflected on how his life's trajectory — from a childhood disrupted by fascism to a career at the pinnacle of scientific achievement — was marked by both hardship and opportunity. His family background in Vienna, a city that had long been a center of intellectual and scientific life, may have contributed to the academic orientation that characterized his later pursuits.

As a young man in the United States, Karplus demonstrated aptitude in science and mathematics, which would lead him to pursue undergraduate studies at Harvard University.

Education

Karplus received his undergraduate degree from Harvard University in 1951. He then pursued graduate studies at the California Institute of Technology (Caltech), where he worked under the supervision of Linus Pauling, one of the most influential chemists of the twentieth century and himself a two-time Nobel laureate. At Caltech, Karplus completed his doctoral dissertation on the bifluoride ion, earning his Ph.D. in 1954. The mentorship of Pauling, who was renowned for applying quantum mechanics to chemical bonding, had a formative influence on Karplus's approach to theoretical chemistry. Pauling's emphasis on using theoretical frameworks to understand the structures and properties of molecules helped orient Karplus toward the computational and theoretical methods that would define his career.

Following his doctoral work, Karplus held postdoctoral and early faculty positions before joining the faculty at Harvard University, where he would spend the bulk of his academic career.

Career

Early Academic Career and the Karplus Equation

Karplus began his academic career in the 1950s, a period during which theoretical chemistry was beginning to benefit from advances in quantum mechanics and, increasingly, from the emergence of digital computing. Early in his career, Karplus made a significant contribution that would bear his name: the Karplus equation. This equation describes the relationship between the dihedral angle of a molecule and the vicinal coupling constant observed in nuclear magnetic resonance (NMR) spectroscopy. The Karplus equation became an essential tool for chemists seeking to determine the three-dimensional structures of molecules, particularly in organic chemistry and biochemistry. It remains one of the foundational relationships in NMR spectroscopy and is cited in textbooks and research papers across multiple scientific disciplines.

Harvard University

Karplus joined the faculty of Harvard University, where he held the Theodore William Richards Professorship of Chemistry, one of the most distinguished chairs in the department. He remained affiliated with Harvard for the remainder of his career, eventually becoming professor emeritus.

At Harvard, Karplus built a large and active research group that focused on the application of theoretical and computational methods to chemical and biological problems. His group attracted doctoral students, postdoctoral researchers, and visiting scientists from around the world. Over the course of his career, Karplus mentored hundreds of scientists, many of whom went on to hold faculty positions and leadership roles in academia and industry. Former students and colleagues recalled his mentorship as demanding but deeply engaged. According to the Harvard Crimson, Karplus was remembered as an "attentive mentor" who took a close interest in the development of his students' scientific thinking and careers.

Karplus's research at Harvard encompassed a broad range of topics in theoretical chemistry, including quantum mechanical calculations, molecular dynamics simulations, and the development of computational methods for studying the structure and function of proteins, enzymes, and other biological macromolecules. His publication record was extensive, spanning several decades and covering work in physical chemistry, chemical physics, and biophysics.

Development of Multiscale Models

The work for which Karplus is most recognized — and for which he received the Nobel Prize — was his role in the development of multiscale models for complex chemical systems. Beginning in the 1970s, Karplus and his collaborators developed methods that combined classical and quantum mechanical approaches to simulate how molecules behave during chemical reactions. This hybrid approach, known as QM/MM (quantum mechanics/molecular mechanics), allowed researchers to model large biological systems — such as enzymes and proteins — with a level of detail that had not previously been possible.

In the QM/MM approach, the region of a molecule where a chemical reaction takes place is treated using quantum mechanics, which can capture the making and breaking of chemical bonds, while the surrounding molecular environment is treated using the less computationally demanding methods of molecular mechanics. This combination enabled the simulation of chemical processes in systems containing thousands or even millions of atoms, which would have been computationally infeasible using quantum mechanical methods alone.

Karplus's development of these methods was closely linked to the parallel rise of computer technology. In the 1960s and 1970s, computers were still relatively primitive by modern standards, and the application of computational methods to chemistry was viewed with skepticism by many experimentalists. Karplus was among the scientists who recognized the potential of computers to serve as a "computational microscope" — a tool for observing molecular behavior that could not be seen directly through experiment. As computing power grew, the methods developed by Karplus and others became increasingly practical and influential.

The New York Times obituary described Karplus as a chemist "who made early computers a tool" for understanding complex chemical systems, highlighting his role in establishing computational chemistry as a mainstream scientific discipline. Over time, the methods he developed became standard tools in drug design, materials science, and biochemistry, used by researchers worldwide to study everything from protein folding to enzyme catalysis.

University of Strasbourg

In addition to his position at Harvard, Karplus maintained a long-standing affiliation with the University of Strasbourg in France. He served as director of the Biophysical Chemistry Laboratory, a joint laboratory between the French National Centre for Scientific Research (CNRS) and the University of Strasbourg. This dual appointment reflected both his international stature and his commitment to fostering scientific collaboration across national boundaries. His work in Strasbourg contributed to the development of computational chemistry in Europe and strengthened ties between American and French scientific institutions.

CHARMM and Molecular Dynamics

Among Karplus's most significant practical contributions was his involvement in the development of CHARMM (Chemistry at HARvard Macromolecular Mechanics), a widely used molecular dynamics simulation program. CHARMM was designed to model the physical movements of atoms and molecules over time, enabling researchers to simulate the dynamic behavior of proteins, nucleic acids, lipids, and other biological macromolecules. The program and its associated force field became one of the most widely adopted tools in computational biology and biophysics, used in thousands of published studies and by pharmaceutical companies in the process of drug discovery.

Karplus's work on molecular dynamics extended the methods originally developed by Berni Alder and others for simple systems, applying them to the complex and biologically relevant molecules that are central to life processes. His 1977 paper on molecular dynamics simulations of a protein (bovine pancreatic trypsin inhibitor), co-authored with J. Andrew McCammon and Bruce Gelin, is considered a landmark in the field.

Personal Life

Karplus held dual Austrian and American citizenship throughout his life. He died on December 28, 2024, at his home in Cambridge, Massachusetts, at the age of 94.

In addition to his scientific career, Karplus was an accomplished photographer. He maintained a personal website devoted to his photography, which featured images from his travels and daily life. In 2015, the Harvard Gazette published a feature on Karplus's photographic work, noting that he had pursued photography as a serious avocation alongside his scientific research.

Karplus was described by colleagues and former students as intellectually rigorous and deeply committed to the advancement of science. The Harvard Crimson noted that he was remembered not only for his scientific achievements but also for the personal attention he devoted to his students and collaborators.

Recognition

Karplus received numerous awards and honors over the course of his career. The most prominent was the 2013 Nobel Prize in Chemistry, which he shared with Michael Levitt and Arieh Warshel. The Nobel Committee cited their work "for the development of multiscale models for complex chemical systems," recognizing the trio's contributions to computational methods that allowed researchers to simulate chemical processes in complex molecular environments.

In addition to the Nobel Prize, Karplus received the Award in Theoretical Chemistry from the American Chemical Society in 1993. He was elected to the United States National Academy of Sciences and was named a foreign member of the Royal Netherlands Academy of Arts and Sciences.

At the time of his Nobel Prize announcement, Harvard's then-president Drew Gilpin Faust praised Karplus's contributions, and the university held a press conference celebrating his achievement.

Legacy

Martin Karplus's legacy rests on his role in establishing computational chemistry as a central discipline within the chemical sciences. Before the work of Karplus and his contemporaries, chemistry was predominantly an experimental science; theoretical predictions about molecular behavior were limited in scope and accuracy. Through the development of QM/MM methods, molecular dynamics simulations, and tools like CHARMM, Karplus helped create a new paradigm in which computer simulations could complement and, in some cases, guide experimental research.

The methods Karplus developed have had broad applications. In pharmaceutical research, molecular dynamics simulations are routinely used to study how drug molecules interact with their biological targets, accelerating the process of drug discovery. In structural biology, the Karplus equation remains an essential tool for interpreting NMR data. In materials science, the computational approaches pioneered by Karplus and others have been applied to the design of new materials with specific properties.

Karplus's influence extended beyond his own research through the many scientists he trained. His former students and postdoctoral researchers went on to establish their own research groups and to make independent contributions to theoretical and computational chemistry. The Harvard Gazette described him as a "pioneering figure in theoretical chemistry" whose impact was felt across multiple generations of scientists.

The Caltech obituary noted that Karplus's trajectory — from a child fleeing Nazi-occupied Austria to a Nobel Prize–winning scientist — exemplified the contributions of immigrant scientists to American science and education. His dual career in the United States and France further reflected his international orientation and his belief in the value of cross-border scientific collaboration.

Chemical & Engineering News summarized his career as one that "transformed the way chemists think about molecules," noting that his computational methods had become indispensable tools for researchers in chemistry, biology, and medicine.