“Molecular Mayhem! Dynamics, Defects and Disorder:
Modeling Biomacromolecules with Supercomputers”
Dr. Sarah A. Harris, University of Leeds
Presented in conjunction with the departments of Physics and Molecular and Cell Biology
Computational models have huge potential to provide insight into molecular biology by providing detailed animations of biomolecules and their interactions. In principle, these simulations act as a “computational microscope,” so long as the results obtained can be validated against experimental data. Molecular simulation can show how the shapes of biomolecules change due to their thermal motion, how the structure of individual biomolecules is affected by subjecting them to mechanical stress and the possible biological consequences of conformational diversity. However, the computational expense of the calculations, which require high-performance supercomputer facilities, places serious limitations on the length and time-scales that can be accessed. I shall describe the successes and the challenges of simulations of biomacromolecules using examples from our own research, namely DNA packing and recognition and protein aggregation. I will then present a new algorithm we are developing that uses continuum mechanics to model biomolecules that are too large to be simulated at the atomistic level. I will conclude by commenting on future prospects for computer simulation in molecular biology.
Sarah Harris obtained a degree in physics from the University of Oxford before obtaining a PhD in computational chemistry from the School of Pharmacy in Nottingham. She is currently a lecturer in biological physics at the University of Leeds. Her research uses high-performance supercomputing to model the physics of biological macromolecules, with the aim of addressing biological questions. Current research projects use theoretical models of proteins and nucleic acids to understand how biomolecules recognize each other and how these interactions might be modified by drug molecules, how biomolecules act as “molecular switches” through changes in shape and flexibility, how DNA and RNA is packaged and controlled within the cell, and why proteins aggregate into amyloid fibrils. She currently supervises five PhD students working on biomolecular simulation. She teaches undergraduate courses in statistical mechanics, the physics of materials and computational modeling.