Structural Dynamics of Free Proteins in Diffraction.

Among the macromolecular patterns of biological significance, right-handed a-helices are perhaps the most abundant structural motifs. Here, guided by experimental findings, we discuss both ultrafast initial steps and longer-time-scale structural dynamics of helix-coil transitions induced by a range...

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Publicado en:Journal of the American Chemical Society Vol. 133; no. 42; pp. 17072 - 17087
Autores principales: Lin, Milo M., Shorokbov, Dmitry, Zewail, Ahmed H.
Formato: Artículo
Publicado: American Chemical Society 10/26/2011
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Acceso en línea:Ver este registro en EBSCOhost
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      dt: 10/26/2011
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      pub: American Chemical Society
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        10.1021/ja207722k
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        atl: Structural Dynamics of Free Proteins in Diffraction.
      aug:
        au:
          Lin, Milo M.
          Shorokbov, Dmitry
          Zewail, Ahmed H.
        affil: Physical Biology Center for Ultrafast Science and Technology, Arthur Amos Noyes Laboratory for Chemical Physics, California Institute of Technology, Pasadena, California 91125, United States
      su:
        Structural dynamics
        Optical diffraction
        Helices (Algebraic topology)
        Thymosin
        Polypeptides
      sug:
        subj:
          Structural dynamics
          Optical diffraction
          Helices (Algebraic topology)
          Thymosin
          Polypeptides
      ab: Among the macromolecular patterns of biological significance, right-handed a-helices are perhaps the most abundant structural motifs. Here, guided by experimental findings, we discuss both ultrafast initial steps and longer-time-scale structural dynamics of helix-coil transitions induced by a range of temperature jumps in large, isolated macromolecular ensembles of an a-helical protein segment thymosin β (Tβ), and elucidate the comprehensive picture of (un)folding. In continuation of an earlier theoretical work from this laboratory that utilized a simplistic structure-scrambling algorithm combined with a variety of self-avoidance thresholds to approximately model helix-coil transitions in Tβ, in the present contribution we focus on the actual dynamics of unfolding as obtained from massively distributed ensemble-convergent MD simulations which provide an unprecedented scope of information on the nature of transient macromolecular structures, and with atomic-scale spatiotemporal resolution. In addition to the use of radial distribution functions of ultrafast electron diffraction (UED) simulations in gaining an insight into the elementary steps of conformational interconversions, we also investigate the structural dynamics of the protein via the native (a-helical) hydrogen bonding contact metric which is an intuitive coarse graining approach. Importantly, the decay of a-helical motifs and the (globular) conformational annealing in Tβ occur consecutively or competitively, depending on the magnitude of temperature jump.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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