Editorial pubs.acs.org/JCTC
A Reflection on Klaus Schulten
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and later NAnoscale Molecular Dynamics). For this, he forged an unlikely partnership with computer scientist Laxmikant Kalé and began a two-decades-long journey with the National Center for Supercomputing Applications (NCSA), located just a few blocks from his lab. NAMD went on to win the 2002 Gordon Bell Award and the 2012 Sidney Fernbach Award. From 1990 until his death, Klaus was director of the Theoretical and Computational Biophysics Group, housed in the Beckman Institute at UIUC. He led a team that rewrote NAMD in C++, with a clever parallelization algorithm to enable tremendous performance gains for systems of appreciable size and complexity. Tackling such systems with much larger numbers of atoms and their dynamical snapshots forced him to create his own visualization program, VMD (for Visual Molecular Dynamics), which he described as a “tool to help us think”. After 13 years of intense work, in 2003 his group hosted a summer school that resulted in a series of online tutorials addressing various topics in molecular simulation. These tutorials were the first of their kind and trained not only the 90 students who made it to Urbana that summer but also legions of researchers around the world. Other molecular dynamics codes followed suit. What resulted was a “phase change” in terms of a new ethic about the importance of sharing information, protocols, and methods for molecular dynamics: The generation of simulation scientists emerging at that time thus became instilled with the idea that you serve not only yourself and your science but also your scientific community. NAMD and VMD became proxies through which Klaus could scale his dreams of scientific discovery through the hands and minds of more than 300,000 registered software users. In spite of frequent suggestions to sell his software, Klaus refused. He was driven not by money or material gain but by scientific advancement. In service to that ideal, for more than 25 years he made his software freely available to the scientific community. Discoveries made with these tools have had untold impact, spanning a broad range of disciplines from basic science to drug discovery to nanoengineering and many fields in between. Klaus’ own scientific contributions were both broad and deep. He dramatically advanced our understanding of the biophysics of magnetoreception that allows birds to navigate during flight. He spent a significant portion of his life dedicated to unraveling the detailed mysteries of photosynthesis, from helping to illuminate new structural and electron transport properties in the light harvesting complex II to modeling the dynamics of an entire chromatophore. He developed steered molecular dynamics as the computational equivalent of atomic force microscopy and used this new tool to investigate muscle contraction and protein folding intermediates. He helped discover how oppositely oriented water molecules act as a selectivity filter in aquaporins and, in the process, contributed mathematical insights that improved the practical application of Jarzynski’s identity in order to extract equilibrium free energies from repeated nonequilibrium pulling experiments. He invented molecular dynamics flexible
his is a guest editorial submitted by Prof. Rommie Amaro. Science has lost a luminary: After an unexpected illness, Klaus Schulten passed away on Halloween morning. He was just 69. I was personally very fortunate to have had Klaus as a close scientific mentor, revered colleague, and adopted doktorvater and offer this remembrance at his passing. Klaus was a scientist who defied classification: He was a physicist, a chemist, a biologist, a mathematician, a theorist, and a computer scientist. He grew up in the Swabia region of southwestern Germany, earning his diplom in physics from the University of Muenster, Germany (1969) and his Ph.D. in chemical physics from Harvard (1974) working under advisor Martin Karplus. He completed his habilitation at the Max Planck Institute for Biophysical Chemistry in Gottingen and, in 1980, became a professor of theoretical physics at the Technical University of Munich (TUM). In retrospect, this time period proved to be seminal for the field of molecular dynamics simulations. In 1977, Harvard contemporaries Bruce Gelin and Andy McCammon, together with Karplus, their advisor, took the bold step of developing a program that enabled the application of Newton’s equations of motion, solved numerically on computers, to resolve the timedependent dynamics of atoms within biological structures. Inspired by this work, Klaus pivoted his previously purely theoretical efforts toward computation, and, thus, his love affair with computational biophysics began. As in all lasting love affairs, unrelenting passion and serendipitous encounters would intertwine to change the course of (scientific) history. Klaus, who believed in other people’s talents as much as in his own dreams, joined with Helmut Grubmuller, one of his first graduate students, and Helmut Heller, a computing guru at TUM, to take a serious foray into scientific computing. Together, the trio built a homemade parallel computing chip, the Transputer T60, and wrote a parallel molecular dynamics code, harmonizing chip and algorithm development, with an eye on biological applications. This natural synergy, unappreciated before, between hardware and software development and biological/chemical application would form the cornerstone of Klaus’ career. History continued to present opportunities, which Klaus masterfully seized. In 1987, four years after Larry Smarr delivered his infamous “black proposal” to the National Science Foundation that prodded development of the US supercomputer centers program, Klaus returned to the US to begin his professorship at the University of Illinois, Urbana−Champaign (UIUC). He brought his T60 parallel computing chip in his backpack, accompanied by his dream of a computational microscope through which he imagined exploring the atomic motions of ever-morecomplex systems. By 1990, he convinced the National Institutes of Health to invest in his vision to develop a scalable computer code for molecular dynamics simulations that would take advantage of the emerging supercomputing power. This code later became known as NAMD (originally for Not Another Molecular Dynamics code © XXXX American Chemical Society
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DOI: 10.1021/acs.jctc.6b01111 J. Chem. Theory Comput. XXXX, XXX, XXX−XXX
Journal of Chemical Theory and Computation
Editorial
fitting to improve our ability to connect to cryo-electron microscopy data and used the new algorithm to advance our understanding of numerous macromolecular complexes including the ribosome, viruses, and the 26S proteasome. The impact of Klaus’ many scientific contributions, including over 680 published papers in fields spanning a huge range of disciplines, is undisputed. It is easy to focus on Klaus’ many scientific achievements, his more than 85,000 citations, and the many accolades of his career, but they were based on a great deal of sacrifice. He worked punishing hours for decades, many times choosing to sacrifice his own physical and emotional health in pursuit of his dream. The renewals and site visits of his P41 resource would push Klaus and his team to limits that he redefined and extended with each subsequent round. As a founding member of the “P41 Directors’ Club,” Klaus became known as the “Site Visit King,” receiving a nearly unheard-of perfect score in what would be destined to become the fifth and final renewal that he alone would lead. I had the pleasure of visiting Klaus and his resource in April of this year, during the time when they were nearing submission of their sixth renewal proposal. Klaus would not even consider scheduling the surgery he needed until after the renewal was submitted. Many who have read this final proposal believe that Klaus outlined what was arguably his strongest and most forward-looking vision yet. While Klaus was a visionary who understood how to push computational biophysics to new places, he was also known for his personal charm. He could delightfully become as giddy as a schoolboy when faced with a delicious new scientific challenge. In these moments, one could not help but be swept up in his infectious enthusiasm anticipating an exciting scientific discovery. This sense of wonder and amazement, which came so naturally to Klaus, fueled his endless pursuit of a new and evermore-exacting version of truth. His spirit and excitement were gifts passed on to his many collaborators, students, postdocs, and colleagues. Klaus taught those he worked with to dream big and not to fear scientific risk-taking but rather, embrace it. His passion and love for computational chemistry and biophysics were sometimes misunderstood. Klaus was renown for his fierceness and his unwavering commitment to excellence in scientific research. He was his own harshest critic, and he inspired those he worked with to do the same. With his students, postdocs, and collaborators, he practiced tough love. Most students would later recall a rite of passage in which a group meeting they presented in would become a baptism by fire, during which one tried not to crack under his intense line of questioning and his uncompromising expectations. Somehow, with the passage of time, these moments that seemed so difficult would become cherished memories, akin to scientific strength training. From his earliest days and until the very end, Klaus fought to create a world in which computation would be met with the same respect as pure theory. Viewed as even more heretical was Klaus’ idea that the computational microscope was yet another form of experimentation. Klaus shouldered much of this burden, which at times must have seemed tremendous if not unbearable. He did so without compromise or complaint, because of his unwavering commitment to one central goal − his belief that one could use physical, mathematical, and computational means to give new insights into the physics of living cells. Although remnants of the tensions between theory and computation still exist today, they are significantly less apparent, in large part because of Klaus’ hard-fought efforts. As for his unconventional notion of computation as an alternate form of experimentation − this ideal will
undoubtedly be furthered through the continued efforts of our community. Every good love story has a happy ending, and this one is no different. For me, and for many of us who knew Klaus, there is a palpable pain from knowing that he will not get to see this happy ending in the flesh, yet we all know how this story ends. It is almost easy to imagine how it unfolds. His dream of simulating whole cells, with all their baffling and intricate complexity, their many piece parts working together to provide the timedependent dynamics that create and sustain life, the wiggling and jiggling of all their atomic movements, illuminating new mysteries and phenomena that, without Klaus’ influence, might not ever have been imagined. This is the legacy Klaus leaves us, that we are propelled toward; the happy ending made possible because we stand on the shoulders of this brilliant, courageous, and caring man, this giant who came before us.
Rommie E. Amaro*
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Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, United States
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Corresponding Author
*E-mail:
[email protected]. Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS.
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DOI: 10.1021/acs.jctc.6b01111 J. Chem. Theory Comput. XXXX, XXX, XXX−XXX
