The folding pathway of ubiquitin from all-atom molecular dynamics simulations

Biophysical Chemistry
Neelan J Marianayagam, Sophie E Jackson

Abstract

The folding (unfolding) pathway of ubiquitin is probed using all-atom molecular dynamics simulations. We dissect the folding pathway using two techniques: first, we probe the folding pathway of ubiquitin by calculating the evolution of structural properties over time and second, we identify the rate determining transition state for folding. The structural properties that we look at are hydrophobic solvent accessible surface area (SASA) and Calpha-root-mean-square deviation (rmsd). These properties on their own tell us relatively little about the folding pathway of ubiquitin; however, when plotted against each other, they become powerful tools for dissecting ubiquitin's folding mechanism. Plots of Calpha-rmsd against SASA serve as a phase space trajectories for the folding of ubiquitin. In this study, these plots show that ubiquitin folds to the native state via the population of an intermediate state. This is shown by an initial hydrophobic collapse phase followed by a second phase of secondary structure arrangement. Analysis of the structure of the intermediate state shows that it is a collapsed species with very little secondary structure. In reconciling these observations with recent experimental data, the transition that we...Continue Reading

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