Function and dynamics of macromolecular complexes explored by integrative structural and computational biology

• Published in: Current opinion in structural biology Vol. 27; pp. 138 - 148
• Main Authors: Purdy, Michael D, Bennett, Brad C, McIntire, William E, Khan, Ali K., Kasson, Peter M, Yeager, Mark
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2014
• Subjects: Animals; Computational Biology - methods; Humans; Macromolecular Substances - chemistry; Macromolecular Substances - metabolism; Protein Structure, Secondary; Protein Structure, Tertiary; Ribosomes - chemistry; Ribosomes - metabolism
• ISSN: 0959-440X; 1879-033X
• DOI: 10.1016/j.sbi.2014.08.006

•EM, X-ray crystallography and MD simulation comprise an integrative approach to explore macromolecular complexes.•Three vignettes are described: structure, function and dynamics of ribosomes, the Arp2/3–actin complex and the β2-adrenergic receptor–Gs protein complex.•Recent technical advancements create unprecedented synergies for integrative structural and computational biology. 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.