title: Local Fluctuations and Conformational Transitions in Proteins.
abstract: 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 interacting with their cognate proteins. Hence, T-pad might be a useful tool for the investigation of interactions between proteins and their cellular partners at the genome-wide level.
authors.affiliation: CNR-Institute of Crystallography, via Amendola 122/o, I-70126, Bari, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Caliandro
authors.affiliation: Institute for Research in Biomedicine and Barcelona Supercomputing Center, Joint Research Program on Computational Biology, Baldiri I Reixac 10, 08028, Barcelona, Spain.|Jülich Supercomputing Centre, Institute for Advanced Simulation, Forschungszentrum Jülich, D-52425 Jülich, Germany.|Computational Biophysics, German Research School for Simulation Sciences 1, D-52425 Jülich, Germany, and Institute for Advanced Simulation, Forschungszentrum Jülich, D-52425 Jülich, Germany.
authors.forename: Giulia
authors.initials: G
authors.lastname: Rossetti
authors.affiliation: Computational Biophysics, German Research School for Simulation Sciences 1, D-52425 Jülich, Germany, and Institute for Advanced Simulation, Forschungszentrum Jülich, D-52425 Jülich, Germany.|Statistical and Biological Physics Sector, International School for Advanced Studies (SISSA), Trieste, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni