title: Bayesian inference of protein ensembles from SAXS data.
abstract: The inherent flexibility of intrinsically disordered proteins (IDPs) and multi-domain proteins with intrinsically disordered regions (IDRs) presents challenges to structural analysis. These macromolecules need to be represented by an ensemble of conformations, rather than a single structure. Small-angle X-ray scattering (SAXS) experiments capture ensemble-averaged data for the set of conformations. We present a Bayesian approach to ensemble inference from SAXS data, called Bayesian ensemble SAXS (BE-SAXS). We address two issues with existing methods: the use of a finite ensemble of structures to represent the underlying distribution, and the selection of that ensemble as a subset of an initial pool of structures. This is achieved through the formulation of a Bayesian posterior of the conformational space. BE-SAXS modifies a structural prior distribution in accordance with the experimental data. It uses multi-step expectation maximization, with alternating rounds of Markov-chain Monte Carlo simulation and empirical Bayes optimization. We demonstrate the method by employing it to obtain a conformational ensemble of the antitoxin PaaA2 and comparing the results to a published ensemble.
authors.affiliation: Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen N, Denmark. lubo.antonov@gmail.com thamelry@binf.ku.dk.
authors.forename: L D
authors.initials: LD
authors.lastname: Antonov
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg, Vladimir-Prelog-Weg 2, CH-8093 Zürich, Switzerland and Institute for Research in Biomedicine, Università della Svizzera Italiana, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Olsson
authors.affiliation: Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: W
authors.initials: W
authors.lastname: Boomsma
authors.affiliation: Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen N, Denmark. lubo.antonov@gmail.com thamelry@binf.ku.dk.
authors.forename: T
authors.initials: T
authors.lastname: Hamelryck
mesh_terms: D001499:Bayes Theorem; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D064267:Intrinsically Disordered Proteins