Rigidity versus flexibility: the dilemma of understanding protein thermal stability

  • Andrey Karshikoff
    Department of Biosciences and Nutrition Karolinska Institutet Huddinge Sweden
  • Lennart Nilsson
    Department of Biosciences and Nutrition Karolinska Institutet Huddinge Sweden
  • Rudolf Ladenstein
    Department of Biosciences and Nutrition Karolinska Institutet Huddinge Sweden

書誌事項

公開日
2015-07-15
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1111/febs.13343
公開者
Wiley

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説明

<jats:p>The role of fluctuations in protein thermostability has recently received considerable attention. In the current literature a dualistic picture can be found: thermostability seems to be associated with enhanced rigidity of the protein scaffold in parallel with the reduction of flexible parts of the structure. In contradiction to such arguments it has been shown by experimental studies and computer simulation that thermal tolerance of a protein is not necessarily correlated with the suppression of internal fluctuations and mobility. Both concepts, rigidity and flexibility, are derived from mechanical engineering and represent temporally insensitive features describing static properties, neglecting that relative motion at certain time scales is possible in structurally stable regions of a protein. This suggests that a strict separation of rigid and flexible parts of a protein molecule does not describe the reality correctly. In this work the concepts of mobility/flexibility versus rigidity will be critically reconsidered by taking into account molecular dynamics calculations of heat capacity and conformational entropy, salt bridge networks, electrostatic interactions in folded and unfolded states, and the emerging picture of protein thermostability in view of recently developed network theories. Last, but not least, the influence of high temperature on the active site and activity of enzymes will be considered.</jats:p>

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