When you think of biomedical research, you might picture a scientist in a lab coat, hovering over a microscope or culturing cells in a petri dish. This kind of “wet lab” work is an important part of science but it’s not the only kind. Increasingly, many scientists forgo the lab coat for high-performance computers and innovative software programs. These scientists work in what is called a “dry lab” – a term to describe research and analysis that is done with computers outside of the traditional lab environment.
Dr. Brad Dickson, a computational biophysicist in Dr. Scott Rothbart’s lab, uses the Institute’s high-performance computing capabilities and other advanced technology to delve into the world of proteins and other molecules at the atomic level. Other tools in his arsenal include mathematical calculations, algorithms and physical laws of nature, which he harnesses to uncover and understand the complex scientific questions. He works on a team that comprises experts from many scientific backgrounds and disciplines. Together, their research creates a holistic picture of molecular interactions that often are the basis for the development of new diagnostics and therapies.
It’s a unique approach. Most people don’t think of physics when they think of cancer or neurodegenerative disease research, but the elements that govern the observable world also play a significant role in physical interactions at the atomic level.
“There are long-range cosmological forces that describe planetary interactions and there are short-range forces that describe interactions between particles, like electrons going around atoms,” Dickson said. “Knowledge of these forces allows us to simulate planetary motions, and it allows us to simulate protein-protein and protein-ligand interactions.”
Combining these forces with Newton’s second law (F=ma) and the Institute’s high performance massively parallel computing resources allows Dickson to simulate protein-protein and protein-drug interactions. The therapeutic and functional impact of disease-related mutations can be explored in this virtual world to better inform future experiment design. Dickson is like a writer who gathers information on his characters, their lives, their physical limitations and proclivities – then writes the story of how they will function in their world. Only in this case, the characters are atomic-level molecules rather than people, and the stories aren’t entertainment but clues to the mysteries of cancer and other diseases.
Being able to simulate biochemical interactions is complex work that involves the right technology and infrastructure, but Dickson views his dry lab work as being a time saver and an efficient way to conduct experiments.
“A dry lab is a place to generate hypotheses and do it cheaply and efficiently,” Dickson said. “The materials costs are low if you have a high-performance computer, and it’s really an efficient way to explore current hypotheses and discover new ones.”
In the next 10 years, Dickson believes technology and software will give scientists the ability to simulate atomic-level interactions involving large proteins, nucleosomes and pieces of chromatin – a complex of DNA and proteins that form chromosomes.
“Questions at the intersection of chromatin biology and disease are increasingly complex, involving multiple protein complexes as well as nucleosomes and stretches of DNA. Correspondingly, computation is being pushed to keep up as this is often the only way to bridge the atomistic world with the experimental data. With the technology and software constantly being developed, in the next decade I think we will be able to work on incredibly large systems,” Dickson said.
Dickson’s work in physics and molecular dynamics plays a crucial role in the modern world of biomedical research. By understand the physical forces of molecular interactions, Institute scientists are discovering new ways to uncover the mysteries of cancer and neurodegenerative diseases – and helping to bring forth new diagnostics and therapies for patients.