title: Characterization of protein flexibility using small-angle x-ray scattering and amplified collective motion simulations.
abstract: Large-scale flexibility within a multidomain protein often plays an important role in its biological function. Despite its inherent low resolution, small-angle x-ray scattering (SAXS) is well suited to investigate protein flexibility and determine, with the help of computational modeling, what kinds of protein conformations would coexist in solution. In this article, we develop a tool that combines SAXS data with a previously developed sampling technique called amplified collective motions (ACM) to elucidate structures of highly dynamic multidomain proteins in solution. We demonstrate the use of this tool in two proteins, bacteriophage T4 lysozyme and tandem WW domains of the formin-binding protein 21. The ACM simulations can sample the conformational space of proteins much more extensively than standard molecular dynamics (MD) simulations. Therefore, conformations generated by ACM are significantly better at reproducing the SAXS data than are those from MD simulations.
authors.affiliation: Hefei National Laboratory for Physical Science at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wen
authors.affiliation: Hefei National Laboratory for Physical Science at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Peng
authors.affiliation: Advanced Photon Source, Argonne National Laboratory, Chicago, Illinois.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Hefei National Laboratory for Physical Science at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Gong
authors.affiliation: Hefei National Laboratory for Physical Science at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China. Electronic address: zzyzhang@ustc.edu.cn.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D017122:Bacteriophage T4 / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry*; D003198:Computer Simulation; D004548:Elasticity; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009038:Motion; D009113:Muramidase / Q000737:chemistry; D009687:Nuclear Proteins / Q000737:chemistry*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D016601:RNA-Binding Proteins; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; C485420:WBP4 protein, human; D009113:Muramidase