Conformational Space of Flexible Biological Macromolecules from Average Data.

The concept of maximum occurrence (MO), i.e., the maximum percent of time that flexible proteins can spend in any given conformation, is introduced, and a rigorous method is developed to extensively sample the conformational space and to construct MO maps from experimental data. The method is tested...

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Publicado en:Journal of the American Chemical Society Vol. 132; no. 38; pp. 13553 - 13559
Autores principales: Bertini, Ivano, Giachetti, Andrea, Luchinat, Claudio, Parigi, Giacomo, Petoukhov, Maxim V., Pierattelli, Roberta, Ravera, Enrico, Svergun, Dmitri I.
Formato: Artículo
Publicado: American Chemical Society 9/29/2010
Materias:
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 9/29/2010
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        10.1021/ja1063923
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        atl: Conformational Space of Flexible Biological Macromolecules from Average Data.
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          Bertini, Ivano
          Giachetti, Andrea
          Luchinat, Claudio
          Parigi, Giacomo
          Petoukhov, Maxim V.
          Pierattelli, Roberta
          Ravera, Enrico
          Svergun, Dmitri I.
        affil:
          CERM, University of Florence, Via L. Sacconi 6, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy
          Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy
          EMBL, Hamburg Outstation, Notkestrasse 85, D-22603 Hamburg, Germany
          Institute of Crystallography, Russian Academy of Sciences, Leninsky pr. 59, 117333 Moscow, Russia
      su:
        Biomacromolecules
        Calmodulin antagonists
        Conformational analysis
        Magnetic properties of rare earth metals
        Computer software
        Grid computing
        Nuclear magnetic resonance
        Web portals
      sug:
        subj:
          Biomacromolecules
          Calmodulin antagonists
          Conformational analysis
          Magnetic properties of rare earth metals
          Computer software
          Grid computing
          Nuclear magnetic resonance
          Web portals
      ab: The concept of maximum occurrence (MO), i.e., the maximum percent of time that flexible proteins can spend in any given conformation, is introduced, and a rigorous method is developed to extensively sample the conformational space and to construct MO maps from experimental data. The method is tested in a case study, the flexible two-domain protein calmodulin (CaM), using SAXS and NMR data (i.e., pseudocontact shifts and self-orientation residual dipolar couplings arising from the presence of paramagnetic lanthanide ions), revealing that the "closed" and "fully extended" conformations trapped in the crystalline forms of CaM have MOs of only 5 and 15%, respectively. Compact conformations in general have small MOs, whereas some extended conformations have MO as high as 35%, strongly suggesting these conformations to be most abundant in solution. The method is universally applicable as it requires only standard SAXS data and specific NMR data on lanthanide derivatives of the protein (using native metal sites or lanthanide tagging). The computer program is publicly available using the grid computing infrastructure through the authors' Web portal.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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