Abstract
According to NMR chemical shift data, the ensemble of ubiquitin is a mixture of “open” and “closed” conformations at rapid equilibrium. Pressure perturbations provide the means to study the transition between the two conformers by imposing an additional constraint on the system's partial molar volume. Here we use nanosecond-timescale molecular dynamics simulations to characterize the network of correlated motions accessible to the conformers at low- and high-pressure conditions. Using the isotropic reorientational eigenmode dynamics formalism to analyze our simulation trajectories, we reproduce NMR relaxation data without fitting any parameters of our model. Comparative analysis of our results suggests that the two conformations behave very differently. The dynamics of the “closed” conformation are almost unaffected by pressure and are dominated by large-amplitude correlated motions of residues 23–34 in the extended α-helix. The “open” conformation under conditions of normal pressure displays increased mobility, focused on the loop residues 17–20, 46–55, and 58–59 at the bottom of the core of the structure, as well as the C-terminal residues 69–76, that directly participate in key protein-protein interactions. For the same conformation, a pressure increase induces a loss of separability between molecular tumbling and internal dynamics, while motions between different backbone sites become uncorrelated.
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