Sarah Rauscher
University of Toronto

Editor
Biophysical Reports

At a cocktail party of non-scientists, how would you explain what you do?

We look at proteins as a machine, and we are aiming to describe in precise detail how this machine works, to develop a blueprint. Viruses and bacteria, for example, target specific proteins and bind with them, while protein mutations are involved in diseases like cancer. Treatment design, therefore, often starts with getting a clear understanding of the structure and dynamics of the proteins involved in disease. We are using computer simulations to better understand disordered proteins – proteins without a fixed, static structure. Computational methods are perfectly suited to studying the molecular structures of disordered proteins, which cannot be fully investigated through experiments. By simulating these proteins, in collaboration with people who are working on them using experimental approaches, we can develop a more complete picture of what they look like and how they move. These simulations are computationally challenging and can take on the order of hundreds to thousands of computers for, in some cases, a full year. It took me 8 months to run all of the simulations for my first Ph.D. paper. As computational power increases, we can simulate larger systems for longer times. It’s exciting to see how rapidly the field of computational biophysics is evolving!

What are you currently working on that excites you?

Changes in proteins are at the root of many diseases, and the structure and dynamics of proteins are highly sensitive to even subtle perturbations. For example, disordered proteins are affected by changes in solution conditions, while protein mutations underly various diseases. Simulations offer a powerful tool to describe the effects of different types of perturbations at the molecular level. My lab is currently working on several projects along these lines. For example, we are studying the effect of molecular crowding on the structure and dynamics of fluorescent proteins in collaboration with Eitan Lerner at the Hebrew University of Jerusalem. We are simulating protein motion in a crystal environment in collaboration with Rama Ranganathan at the University of Chicago. Through collaboration, we can relate molecular mechanisms deciphered using computational and in vitro approaches to biological processes in vivo, allowing us to make more rapid progress than any of these approaches could make individually.