Year: 2018
Type: article
Abstract: Wide-angle X-ray solution scattering (WAXS) patterns contain substantial information about the structure and dynamics of a protein. Solution scattering from a rigid protein can be predicted from atomic coordinate sets to within experimental error. However, structural fluctuations of proteins in solution can lead to significant changes in the observed intensities. The magnitude and form of these changes contain information about the nature and spatial extent of structural fluctuations in the protein. Molecular dynamics (MD) simulations based on a crystal structure and selected force field generate models for protein internal motions, and here we demonstrate that they can be used to predict the impact of structural fluctuations on solution scattering data. In cases where the observed and calculated intensities correspond, we can conclude that the X-ray scattering provides direct experimental validation of the structural and MD results. In cases where calculated and observed intensities are at odds, the inconsistencies can be used to determine the origins of these discrepancies. They may be because of overestimates or underestimates of structural fluctuations in MD simulations, under-sampling of the structural ensemble in the simulations, errors in the structural model, or a mismatch between the experimental conditions and the parameters used in carrying out the MD simulation.
Source: Protein Science
DOI: 10.1002/pro.3508
Authors: Hao Zhou, Hugo Guterres, Carla Mattos, Lee Makowski
Institution: Northeastern University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: G1017699072, G102163711, G107546177, G1313983767, G1488452202, G1505794299, G1516381418, G1664757510, G1920558564, G2008846556, G2101401529, The Biophysics Collaborative Access Team, G21810547, G2287611682, G262962599, G2887060908, G3075337988, G340565428, G3589692066, G367921431, G3976199993, G409777406, Operation of the Cornell High Energy Synchrotron Source (CHESS), G4909793234, G498139845, G5106849484, G513797252, G5499275266, G5607048534, G5825187129, G6341728005, G6848031779, G6918803902, G7368700025, Allosteric elements in the superfamily of small GTPases, Macromolecular Diffraction Resource: MacCHESS, G9000264529, G9000275877, G969889393, G993149817
OpenAlex ID: W2891531060