Quantitative FRET studies and integrative modeling unravel the structure and dynamics of biomolecular systems.

Autor: Dimura M; Chair for Molecular Physical Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Peulen TO; Chair for Molecular Physical Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Hanke CA; Chair for Molecular Physical Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Prakash A; Chair for Molecular Physical Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Gohlke H; Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Seidel CA; Chair for Molecular Physical Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany. Electronic address: cseidel@hhu.de.
Jazyk: angličtina
Zdroj: Current opinion in structural biology [Curr Opin Struct Biol] 2016 Oct; Vol. 40, pp. 163-185. Date of Electronic Publication: 2016 Dec 07.
DOI: 10.1016/j.sbi.2016.11.012
Abstrakt: Förster Resonance Energy Transfer (FRET) combined with single-molecule spectroscopy probes macromolecular structure and dynamics and identifies coexisting conformational states. We review recent methodological developments in integrative structural modeling by satisfying spatial restraints on networks of FRET pairs (hybrid-FRET). We discuss procedures to incorporate prior structural knowledge and to obtain optimal distance networks. Finally, a workflow for hybrid-FRET is presented that automates integrative structural modeling and experiment planning to put hybrid-FRET on rails. To test this workflow, we simulate realistic single-molecule experiments and resolve three protein conformers, exchanging at 30μs and 10ms, with accuracies of 1-3Å RMSD versus the target structure. Incorporation of data from other spectroscopies and imaging is also discussed.
(Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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