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Conformational Ensembles from Experimental Data
and Computer Simulations
Sunday Speaker Abstracts
20
Bayesian Refinement of Protein Structures and Ensembles Against SAXS Data by Using
Molecular Dynamics
Jochen Hub
.
Georg-August University Goettingen, Göttingen, Germany.
Small-angle X-ray scattering is an increasingly popular technique used to detect protein
structures and ensembles in solution. However, the refinement of structures and ensembles
against SAXS data is often ambiguous due to the low information content of SAXS data,
unknown systematic errors, and unknown scattering contributions from the solvent. We offer a
solution to such problems by combining Bayesian inference with molecular dynamics
simulations and explicit-solvent SAXS calculations. The Bayesian formulation correctly weights
the SAXS data versus prior physical knowledge, it quantifies the precision or ambiguity of fitted
structures and ensembles, and it accounts for unknown systematic errors due to poor buffer
matching. The method further provides a probabilistic criterion for identifying the number of
states required to explain the SAXS data. The method is demonstrated by refining ensembles of a
periplasmic binding protein and of the large chaperone heat shock protein 90 (Hsp90).
[1] Shevchuk and Hub, Bayesian refinement of protein structures and ensembles against SAXS
data using molecular dynamics, submitted
[2] Chen and Hub, Biophys. J., 108, 2573–2584 (2015), Biophys. J., 107, 435-447 (2014), J.
Phys. Chem. Lett., 6, 5116–5121 (2015)