Local Fluctuations and Conformational Transitions in Proteins.

The intrinsic plasticity of protein residues, along with the occurrence of transitions between distinct residue conformations, plays a pivotal role in a variety of molecular recognition events in the cell. Analysis aimed at identifying both of these features has been limited so far to protein-complex structures. We present a computationally efficient tool (T-pad), which quantitatively analyzes protein residues’ flexibility and detects backbone conformational transitions. T-pad is based on directional statistics of NMR structural ensembles or molecular dynamics trajectories. T-pad is here applied to human ubiquitin (hU), a paradigmatic cellular interactor. The calculated plasticity is compared to hU’s Debye–Waller factors from the literature as well as those from experimental work carried out for this paper. T-pad is able to identify most of the key residues involved in hU’s molecular recognition, also in the absence of its cellular partners. Indeed, T-pad identified as many as 90% of ubiquitin residues in...