title: A Structure-free Method for Quantifying Conformational Flexibility in proteins.
abstract: All proteins sample a range of conformations at physiologic temperatures and this inherent flexibility enables them to carry out their prescribed functions. A comprehensive understanding of protein function therefore entails a characterization of protein flexibility. Here we describe a novel approach for quantifying a protein's flexibility in solution using small-angle X-ray scattering (SAXS) data. The method calculates an effective entropy that quantifies the diversity of radii of gyration that a protein can adopt in solution and does not require the explicit generation of structural ensembles to garner insights into protein flexibility. Application of this structure-free approach to over 200 experimental datasets demonstrates that the methodology can quantify a protein's disorder as well as the effects of ligand binding on protein flexibility. Such quantitative descriptions of protein flexibility form the basis of a rigorous taxonomy for the description and classification of protein structure.
authors.affiliation: Research Laboratory for Electronics, Massachusetts Institute of Technology, 77 Massachusetts Ave. Cambridge MA 02139, USA.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Burger
authors.affiliation: Department of Physics, University of North Florida, 1 University of North Fl Dr, Jacksonville, FL 32224, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Arenas
authors.affiliation: Research Laboratory for Electronics, Massachusetts Institute of Technology, 77 Massachusetts Ave. Cambridge MA 02139, USA.|Electrical Engineering and Computer Science &Institute for Medical Engineering and Science Massachusetts Institute of Technology, 77 Massachusetts Ave. Cambridge MA 02139, USA.
authors.forename: Collin M
authors.initials: CM
authors.lastname: Stultz
mesh_terms: D000465:Algorithms; D001426:Bacterial Proteins / Q000737:chemistry; D066264:Datasets as Topic; D008956:Models, Chemical; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D053838:Scattering, Small Angle; D012996:Solutions; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: D001426:Bacterial Proteins; C068355:CcdA protein, Bacteria; C068356:CcdB protein, Plasmid F; D012996:Solutions