Unfolded-State Dynamics and Structure of Protein L Characterized by Simulation and Experiment.
While several experimental techniques now exist for characterizing protein unfolded states, all-atom simulation of unfolded states has been challenging due to the long time scales and conformational sampling required. We address this problem by using a combination of accelerated calculations on grap...
| Publicado en: | Journal of the American Chemical Society Vol. 132; no. 13; pp. 4702 - 4710 |
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| Autores principales: | , , , , |
| Formato: | Artículo |
| Publicado: |
American Chemical Society
4/7/2010
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| Materias: | |
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=49755397&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 49755397 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 4/7/2010 vid: 132 iid: 13 pid: 997 pub: American Chemical Society artinfo: ui: 49755397 10.1021/ja908369h ppf: 4702 ppct: 8 formats: tig: atl: Unfolded-State Dynamics and Structure of Protein L Characterized by Simulation and Experiment. aug: au: Voelz, Vincent A. Singh, Vijay R. Wedemeyer, William J. Lapidus, Lisa J. Pande, Vijay S. affil: Department of Chemistry, Stanford University, Stanford, California 94305 Department of Physics and Astronomy, Michigan State University, East Lansing, Michigan 48824 Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824 su: Denaturation of proteins Molecular dynamics Chemical research Spectrum analysis Simulation methods & models Equipment & supplies sug: subj: Denaturation of proteins Molecular dynamics Chemical research Spectrum analysis Simulation methods & models Equipment & supplies ab: While several experimental techniques now exist for characterizing protein unfolded states, all-atom simulation of unfolded states has been challenging due to the long time scales and conformational sampling required. We address this problem by using a combination of accelerated calculations on graphics processor units and distributed computing to simulate tens of thousands of molecular dynamics trajectories each up to -∼10 μs (for a total aggregate simulation time of 127 ms). We used this approach in conjunction with Trp-Cys contact quenching experiments to characterize the unfolded structure and dynamics of protein L. We employed a polymer theory method to make quantitative comparisons between high-temperature simulated and chemically denatured experimental ensembles and find that reaction-limited quenching rates calculated from simulation agree remarkably well with experiment. In both experiment and simulation, we find that unfolded-state intramolecular diffusion rates are very slow compared to highly denatured chains and that a single-residue mutation can significantly alter unfolded-state dynamics and structure. This work suggests a view of the unfolded state in which surprisingly low diffusion rates could limit folding and opens the door for all-atom molecular simulation to be a useful predictive tool for characterizing protein unfolded states along with experiments that directly measure intramolecular diffusion. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2010 holdings: @attributes: islocal: N |
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