Abstract

It has been suggested that motions in proteins could be correlated to minimize the net changes to the various energetic contributions that stabilize their native structure. Evidence for motions in proteins has been obtained using molecular dynamics simulations, Nuclear Magnetic Resonance (NMR), fluorescence spectroscopy and single molecule experiments, but the detection of correlations between the motions of residues distant in sequence has remained an elusive goal due of challenges in directly determining time-resolved coordinates from experiment. Recently the combination of NMR data with Molecular Dynamics has been used to characterize protein dynamics at atomic resolution and here we use this approach to probe the dynamics of the protein ubiquitin; by using the large amount of NMR data collected on this protein we have generated a large number of conformations collectively consistent with experiment and validated the resulting ensemble using independent NMR measurements that average on the same timescale. An analysis of the ensemble reveals that the backbone motions of residues distant in sequence but connected by hydrogen bonds are correlated and provides a pathway for the transfer of structural and dynamical information across protein structures, which is the underlying mechanism of binding allostery and folding cooperativity.