Structure of flexible proteins using scattering and simulation

Abstract

Conformational flexibility, manifested as transitions among multiple states accessible to a macromolecular system, is of critical importance to function. Understanding the solution conformational flexibility is challenging: crystallography is inappropriate for this and the application of NMR to large complexes is challenging due to the difficulty in assigning NMR correlations. We have characterized the structure of two flexible proteins: the intrinsically disordered terminal of the c-Src kinase and the Cel7A cellulase. We combined small-angle scattering experiments and molecular dynamics simulations and determined the ensemble of conformations the two proteins sample. We discuss how the integration of scattering and molecular simulations can obtain a complete picture of the relationship between flexible structure and function in complex macromolecular systems. Support or Funding Information “Integrating Small-Angle Neutron Scattering with Molecular Simulation to Determine Structural Ensembles of Complex Biological Systems”. U.S. Department of Energy - Director's Research and Development (LDRD). “Dynamic Visualization of Lignocellulose Degradation by Integration of Neutron Scattering Imaging and Computer Simulation”.U.S. Department of Energy, Office of Biological and Environmental Research (BER) Genomic Science Program. A cellulase (orange) hydrolyzing cellulose (green) in the presence of lignin (brown). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.