TY - JOUR
T1 - An Extended Guinier Analysis for Intrinsically Disordered Proteins
AU - Zheng, Wenwei
AU - Best, Robert B.
N1 - Funding Information:
We thank Attila Szabo for pressing us to consider this problem and for many helpful suggestions. We also thank Joshua Riback and Tobin Sosnick for comments on the manuscript. W.Z. and R.B.B. were supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health ( ZIA DK075104-05 ). W.Z. thanks Arizona State University for the start-up support. This work utilized the computational resources of the NIH HPC Biowulf cluster ( http://hpc.nih.gov ).
PY - 2018/8/3
Y1 - 2018/8/3
N2 - Guinier analysis allows model-free determination of the radius of gyration (Rg) of a biomolecule from X-ray or neutron scattering data, in the limit of very small scattering angles. Its range of validity is well understood for globular proteins, but is known to be more restricted for unfolded or intrinsically disordered proteins (IDPs). We have used ensembles of disordered structures from molecular dynamics simulations to investigate which structural properties cause deviations from the Guinier approximation at small scattering angles. We find that the deviation from the Guinier approximation is correlated with the polymer scaling exponent ν describing the unfolded ensemble. We therefore introduce an empirical, ν-dependent, higher-order correction term, to augment the standard Guinier analysis. We test the new fitting scheme using all-atom simulation data for several IDPs and experimental data for both an IDP and a destabilized mutant of a folded protein. In all cases tested, we achieve an accuracy of the inferred Rg within ∼ 3% of the true Rg. The method is straightforward to implement and extends the range of validity to a maximum qRg of ∼ 2 versus ∼ 1.1 for Guinier analysis. Compared with the Guinier or Debye approaches, our method allows data from wider angles with lower noise to be used to analyze scattering data accurately. In addition to Rg, our fitting scheme also yields estimates of the scaling exponent ν in excellent agreement with the reference ν determined from the underlying molecular ensemble.
AB - Guinier analysis allows model-free determination of the radius of gyration (Rg) of a biomolecule from X-ray or neutron scattering data, in the limit of very small scattering angles. Its range of validity is well understood for globular proteins, but is known to be more restricted for unfolded or intrinsically disordered proteins (IDPs). We have used ensembles of disordered structures from molecular dynamics simulations to investigate which structural properties cause deviations from the Guinier approximation at small scattering angles. We find that the deviation from the Guinier approximation is correlated with the polymer scaling exponent ν describing the unfolded ensemble. We therefore introduce an empirical, ν-dependent, higher-order correction term, to augment the standard Guinier analysis. We test the new fitting scheme using all-atom simulation data for several IDPs and experimental data for both an IDP and a destabilized mutant of a folded protein. In all cases tested, we achieve an accuracy of the inferred Rg within ∼ 3% of the true Rg. The method is straightforward to implement and extends the range of validity to a maximum qRg of ∼ 2 versus ∼ 1.1 for Guinier analysis. Compared with the Guinier or Debye approaches, our method allows data from wider angles with lower noise to be used to analyze scattering data accurately. In addition to Rg, our fitting scheme also yields estimates of the scaling exponent ν in excellent agreement with the reference ν determined from the underlying molecular ensemble.
KW - Guinier analysis
KW - SAXS
KW - intrinsically disordered protein
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U2 - 10.1016/j.jmb.2018.03.007
DO - 10.1016/j.jmb.2018.03.007
M3 - Article
C2 - 29571687
AN - SCOPUS:85044526305
VL - 430
SP - 2540
EP - 2553
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 16
ER -