Lillian Chong, PhD ’02 : A Computational Microscope for Biology

Seeing Proteins in Motion

To see how a protein moves — how it folds, binds, or opens like a pair of jaws — one would need a microscope powerful enough to observe individual atoms in motion. No such instrument exists in a laboratory. So, Lillian Chong built one inside a computer. A professor at the University of Pittsburgh, Chong develops physics-based simulations that reveal biological processes at an atomic level of detail no experiment can match. “We’re basically using a computational microscope,” she says. It’s capable of capturing molecular motions at a millionth of a billionth of a second. Once she built it, she did something equally significant: She gave it away.

From Code to Global Tool

The software at the heart of Chong's work, WESTPA, the Weighted Ensemble Simulation Toolkit, with Parallelization and Analysis, began as one of her graduate student’s Python scripts, revised more than 30 times until it became a tool other labs wanted to use. Chong made it open source, held hands-on workshops, and scaled it up so researchers worldwide could run simulations on supercomputers or university clusters. In the decade since its release, WESTPA has attracted more than 200,000 users across academia, industry, and fields as diverse as astronomy and geology. For drug discovery alone, the implications are significant: Her methods can model how quickly a drug binds to its target and whether it gets inside a cell at all — a common and costly failure point in pharmaceutical development.

COVID Simulations at Supercomputer Scale

During the COVID-19 pandemic, a persistent graduate student at UC San Diego asked Chong whether WESTPA could simulate the coronavirus spike protein, the structure that hinges open to latch onto human cells. Chong hesitated. The system involved more than a million atoms unfolding on a timescale that would strain even the most advanced molecular simulations. It would push WESTPA to an unprecedented scale. The female-led team pressed ahead, producing a landmark paper in Nature Chemistry and winning the inaugural Gordon Bell Special Prize for High-Performance Computing-Based COVID-19 research, widely considered the Nobel Prize of supercomputing. For Chong, the project was proof of something she has built her career around. “Progress in science often happens at the intersection of research areas and between fields,” she says.