A Structure-free Method for Quantifying Conformational Flexibility in proteins

Sci Rep. 2016 Jun 30:6:29040. doi: 10.1038/srep29040.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Bacterial Proteins / chemistry
  • Datasets as Topic
  • Models, Chemical*
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Protein Conformation*
  • Scattering, Small Angle
  • Solutions
  • Thermodynamics
  • X-Ray Diffraction

Substances

  • Bacterial Proteins
  • CcdA protein, Bacteria
  • CcdB protein, Plasmid F
  • Solutions