Simon Mitternacht
Simulating Mechanical Unfolding of Proteins

Master Thesis in Theoretical Physics

Advisors: Anders Irbäck and Sandipan Mohanty

Abstract:
Mechanical protein unfolding is simulated for the F_s peptide and a ubiquitin domain by pulling at both ends with constant force. The transition of F_s from the folded state to the stretched out state as function of force is studied by thermodynamical simulations showing a critical region around 25 pN. On ubiquitin, quasi-kinetic Monte Carlo simulations were run that show a sudden unfolding with exponentially distributed unfolding times which is in agreement with a recent experiment by Schlierf et al. Many details of ubiquitin unfolding, including the nature of the intermediate state that occasionally occurs, are not accessible in the experiment. In this in silico study we investigate them by keeping track of when native contacts break and taking snapshots of the protein during unfolding. Our simulation data indicate a pathway that differs from the one suggested by Schlierf et al. but it is reasonable and consistent with their observations.

LU TP 04-42, January 2005