title: SAXS-Guided Metadynamics.
abstract: The small-angle X-ray scattering (SAXS) methodology enables structural characterization of biological macromolecules in solution. However, because SAXS provides low-dimensional information, several potential structural configurations can reproduce the experimental scattering profile, which severely complicates the structural refinement process. Here, we present a bias-exchange metadynamics refinement protocol that incorporates SAXS data as collective variables and therefore tags all possible configurations with their corresponding free energies, which allows identification of a unique structural solution. The method has been implemented in PLUMED and combined with the GROMACS simulation package, and as a proof of principle, we explore the Trp-cage protein folding landscape.
authors.affiliation: Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University , SE-106 91 Stockholm, Sweden.
authors.forename: Dari
authors.initials: D
authors.lastname: Kimanius
authors.affiliation: Modeling and Structural Biology, Protein Engineering, Global Research, Novo Nordisk A/S , Novo Nordisk Park, DK-2760 Måløv, Denmark.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pettersson
authors.affiliation: Modeling and Structural Biology, Protein Engineering, Global Research, Novo Nordisk A/S , Novo Nordisk Park, DK-2760 Måløv, Denmark.
authors.forename: Gerd
authors.initials: G
authors.lastname: Schluckebier
authors.affiliation: Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University , SE-106 91 Stockholm, Sweden.|Department of Theoretical Physics and Swedish e-Science Research Center, Science for Life Laboratory, KTH Royal Institute of Technology , SE-171 21 Solna, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Lindahl
authors.affiliation: Department of Theoretical Physics and Swedish e-Science Research Center, Science for Life Laboratory, KTH Royal Institute of Technology , SE-171 21 Solna, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Andersson
mesh_terms: D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D053838:Scattering, Small Angle; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: D011506:Proteins