From Abstract to Indispensable
A biologist fascinated by the puzzle of how DNA is packaged into chromosomes and organized in our cells may once have peered into a microscope. Today, they are just as likely to be staring at lines of code on a supercomputer. Equations, computer models and simulations can reveal patterns and possibilities invisible to the eye, offering key insights into some of biology’s most complex puzzles.
Once seen as a niche area separate from experimental work done in the lab, theory is now central to how researchers navigate complexity. The change has been propelled by an explosion in computing power. “Huge calculations were impossible at the start of my career because we just didn’t have the computational power,” said Peter Rossky, Rice’s Harry C. and Olga K. Wiess Professor of Chemistry. “The machines that we have now can do several orders of magnitude more computations in the same amount of time as what we could do just 15 years ago.”
Rice’s Wiess School of Natural Sciences shows how theory can both shape and be shaped by the demands of modern science. Over the past four decades, the school has built a reputation as a leader in theoretical science by investing in groundbreaking fields of theory. According to Gustavo Scuseria, Rice’s Robert A. Welch Professor of Chemistry, the transformation was “driven by hiring top-notch people” and by “a perception from the experimental faculty that theory was important.”
This shift in perception mirrors a broader scientific revolution. In chemistry, physics and biology, powerful models now allow scientists to test ideas before committing to costly or time-consuming experiments. At Rice, these tools have sparked collaborations, built centers and drawn a new generation of faculty and students eager to work at the intersection of ideas and applications.
Former Rice historian Melissa Kean tells the story of the supercomputer known as R1, Rice's first large computational research computer.
Theory That Translates
When Scuseria joined the Rice faculty in 1989, theoretical chemistry was still a specialized field that many experimentalists found difficult to access. At the time, the Department of Chemistry had only one active theorist, John Hutchinson. Scuseria recalled that while he “loved Houston immediately,” the department was “weak in theory” compared to other institutions. He was hired by Dean James Kinsey ’56 ’59, who wanted to strengthen that area, particularly by adding a quantum theorist in the wake of the 1985 discovery of buckyballs.
Scuseria was part of a growing wave of researchers who saw the real power of theory in its ability to advance experiments. In quantum chemistry, that meant developing methods and computational tools that non-specialists could use to answer real chemical questions.
One of Scuseria’s breakthroughs was developing a way to fix a common flaw in Density Functional Theory (DFT), a method that predicts the properties of molecules and materials using only their electron density instead of the far more complex many-electron wave function. DFT calculations worked well for some classes of compounds but were not reliable for many others. His trick of separating short-range and long-range interactions became his HSE functional and part of the widely used Gaussian software package, giving experimental chemists direct access to advanced theoretical methods.
He watched the shift happen in real time. "When I came to Rice, for many years people would come to my office, knock on the door and tell me about their problem, and expect me and my group to collaborate with them,” he said. “That stopped about 20 years ago because they were doing the calculations themselves. Software had evolved to the point that the Gaussian code and many other codes made this possible.”
The ability to put powerful theoretical tools directly into the hands of experimentalists was a fundamental shift and was reinforced by a department culture that valued theory as a partner to experiment, not a separate track.
Theory That Explains Life
The arrival of Anatoly Kolomeisky as an assistant professor of chemistry in 2000 marked another turning point for theory at Rice. A leader in applying statistical mechanics to elucidate the molecular mechanisms of complex chemical and biological systems, he brought a new dimension of theory into the university’s growing biology landscape. “When I arrived, only Gus Scuseria was here,” he recalled. “There was no one else around.”
Kolomeisky’s research tackles problems that are hard to solve at the lab bench alone: cellular transport, motor proteins and molecular motors, protein–DNA interactions and the dynamics of cancer development. Theory offered a way to explore these complex systems, revealing patterns and mechanisms that experiments could then test.
The relationship between theory and experiment, however, runs both ways. “For any theoretical person, it is important to have reliable quantitative experimental measurements and observations that can be used for validation of theoretical ideas,” Kolomeisky said. That was not easy in the early 2000s, when many areas of the biological sciences were still far from quantitative. “New methods, like single-molecule and super-resolution techniques, were just appearing,” he said. “No one at Rice worked in those areas at that time.”
Kolomeisky had to work to actively build his network of collaborators. “I went to more conferences, read more and talked with more people to move the science forward,” he said. “It was not simple, but eventually it was productive. I got to know new people at Rice, the Texas Medical Center and the University of Houston, and that shaped some of my research.”
By steadily cultivating these connections, he helped lay the groundwork for the larger community of theorists that would soon transform Rice’s profile in biological physics.
Theory That Elevates Institutions
The most significant leap in expanding the theory community at Rice came in 2011, when National Academy members José Onuchic, the Harry C. and Olga K. Wiess Professor of Physics and Astronomy, Peter Wolynes, the D.R. Bullard-Welch Foundation Professor of Chemistry, and former Rice professor Herbert Levine, moved the Center for Theoretical Biological Physics (CTBP) from the University of California, San Diego to Rice. This was a landmark moment that elevated the university’s national profile and cemented its role as a hub for interdisciplinary science.
CTBP’s mission is ambitious: to model the most fundamental processes of life, from protein folding to cellular organization, while directly engaging with experimentalists to test predictions. According to Wolynes, the center’s title communicates its aim “towards really fundamental questions, where looking at biological problems brings out new ideas in physics.”
The move to Rice was made possible by the university’s supportive environment and a key Cancer Prevention and Research Institute of Texas (CPRIT) award, which allowed the center to expand its focus into cancer research. Onuchic noted that Rice “provided the right environment” because it “fully understood that the center had to go beyond one department.” He also emphasized the importance of the Texas Medical Center, which offered an “enormous community of experimental research” and a “very fertile environment for us to work together.”
CTBP tackles some of biology’s most difficult problems while continually seeking to grow and expand its areas of research, helping to define the frontier of theoretical biological physics. Wolynes explained, “The focus at the beginning was quite clearly on the molecular scale, because the work on protein folding was still unsolved at that point.” As researchers gained new understanding, they began applying the lessons learned from proteins to questions in chromosome structure and dynamics. “The first part of it was to try to use the style of learning that we had done for proteins and apply it to information about chromosomes,” Wolynes said. “Then, again, we found new things that were ‘Aha’ experiences.” Reflecting on the field as a whole, he added, “It is still a field where there’s an awful lot that we don’t know. It’s good that we don’t know stuff, but we do have some little hints of tools and things that we can do.”
The center is a magnet for top researchers and students drawn to a collaborative environment where boundaries between disciplines are fluid. “We all have appointments in every department,” Onuchic said. “We have students from physics, chemistry, computer science, biosciences and bioengineering. We’ve created an environment that is truly interdisciplinary, where people feel like they should be working together. It has been a very positive thing.”
Theory That Leads
When Peter Rossky — a theoretical chemist and National Academy member known for his atomistic descriptions of water and other liquid-phase systems — became Dean of the School of Natural Sciences in 2014, he brought a clear vision for strengthening the school and ensuring that theory continued to thrive at Rice.
By then, the arrival of the CTBP three years earlier had already elevated Rice’s theory program on the world stage. Rossky saw the impact firsthand. “When I came to Rice 11 years ago, I got emails from Japan and from France saying, ‘You guys have an amazing theory group’ and ‘Rice is doing something phenomenal to pull that many great theorists together.' That gives you a sense of the reach of the impact,” he recalled.
Rossky’s tenure was marked by initiatives that boosted Rice’s research capacity and positioned its scientists at the forefront of their fields. In 2020, he spearheaded the university’s effort to secure a petaflop-scale high-performance computing cluster from AMD. This gift, initially inspired by urgent COVID-19 research needs, tripled Rice’s computing power and continues to enable studies on proteins, genomes, gene regulatory networks and other complex challenges that demand extraordinary computational resources. Available to faculty across all departments, it has become a critical asset for both theorists and experimentalists. As Onuchic put it, “This new computer has been a game-changer for CTBP.”
Rossky also helped lay the groundwork for Rice’s current push into quantum science. He championed a major investment by Rice in quantum information and materials, which has brought in “spectacularly good” faculty across experiment, devices and theory. By uniting expertise across fields, it is positioning Rice to compete — and lead — in the quantum information age.
A look at the high-performance computer donated by AMD, a gift that initially supported COVID-19 research and continues to power groundbreaking science at Rice.
The Power of Theory Done Right
Over the past four decades, Rice has strategically built a theory community that is both deep and broad. From strengthening chemical theory to establishing CTBP at Rice, the university has invested in faculty, centers and infrastructure that connect theory to experiment and foster cross-disciplinary collaboration. These deliberate choices have transformed Rice into a hub where theoretical insight drives discovery.
As Onuchic noted, the way science is done is changing, with three pillars now working together: “theory, experiments and enormous amounts of data.” The new challenge is to understand how these pillars synergize, and that is where Rice has positioned itself as a leader. Onuchic believes this “synergy is how you multiply the science,” breaking down traditional hierarchies and allowing diverse talents to work together to solve complex, important problems.
Looking ahead, Rice continues to model the future of theory in a way that is integrated, collaborative and ambitious. By investing in people, tools and connections across disciplines, the university is shaping a new era in which theoretical insight drives real-world breakthroughs and redefines what science can accomplish.