title: Function and dynamics of macromolecular complexes explored by integrative structural and computational biology.
abstract: Three vignettes exemplify the potential of combining EM and X-ray crystallographic data with molecular dynamics (MD) simulation to explore the architecture, dynamics and functional properties of multicomponent, macromolecular complexes. The first two describe how EM and X-ray crystallography were used to solve structures of the ribosome and the Arp2/3-actin complex, which enabled MD simulations that elucidated functional dynamics. The third describes how EM, X-ray crystallography, and microsecond MD simulations of a GPCR:G protein complex were used to explore transmembrane signaling by the β-adrenergic receptor. Recent technical advancements in EM, X-ray crystallography and computational simulation create unprecedented synergies for integrative structural biology to reveal new insights into heretofore intractable biological systems.
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Purdy
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Brad C
authors.initials: BC
authors.lastname: Bennett
authors.affiliation: Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: McIntire
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Ali K
authors.initials: AK
authors.lastname: Khan
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Center for Membrane Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kasson
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Center for Membrane Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Medicine, Division of Cardiovascular Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: yeager@virginia.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Yeager
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism
chemical_list: D046911:Macromolecular Substances