Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Sunday Speaker Abstracts

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)

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