Evolution of the concept of conformational dynamics of enzyme functions over half of a century: A personal view

Péter Závodszky, István Hajdú

Research output: Contribution to journalReview article

7 Citations (Scopus)


To most physicists, it was always evident that conformational fluctuation is an inherent property of all molecules. Its existence in proteins was mentioned first by Linderström-Lang and Schellman in 1959 based on their hydrogen-deuterium exchange experiments. The "induced fit" mechanism to explain ligand-induced conformational changes was suggested by Koshland in 1958. Straub combined these two concepts in his "fluctuation fit" theory in 1964. The era of protein X-ray crystallography imposed a static view of protein structures. With proteins becoming accessible to NMR analysis, conformational dynamics could be mapped, and a new wave of dynamic interpretation of enzymatic catalysis and molecular recognition appeared. Energy landscapes, energy funnels, conformational selection, conformational distribution shifts are now frequent terms in interpreting biomolecular recognition and enzymatic catalysis. All these interpretations are based on the concept that evolution uses the conformational fluctuations of enzymes to develop efficient and dynamic catalytic machines. In a resurrection of the original "fluctuation fit" concept, it is generally recognized now that spatial and temporal events of catalysis are equally important to describe its mechanism. This special issue, dedicated to the memory of Henryk Eisenberg, prompted us to look back at the last 50 years of development of a concept that - like other important concepts - appeared, evolved and became accepted during the period covered by the scientific lifespan of Henryk. © 2012 Wiley Periodicals, Inc. Biopolymers 99: 263-269, 2013.

Original languageEnglish
Pages (from-to)263-269
Number of pages7
Issue number4
Publication statusPublished - Apr 1 2013



  • allosteric regulation
  • conformational flexibility
  • conformational selection
  • energy landscape
  • protein dynamics

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

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