Barrier crossing in dihydrofolate reductase does not involve a rate-promoting vibration

Mariangela Dametto, Dimitri Antoniou, Steven D. Schwartz

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


We have studied atomic motions during the chemical reaction catalysed by the enzyme dihydrofolate reductase of Escherichia coli (EcDHFR), an important enzyme for nucleic acid synthesis. In our earlier work on the enzymes human lactate dehydrogenase and purine nucleoside phosphorylase, we had identified fast sub-ps motions that are part of the reaction coordinate. We employed Transition Path Sampling (TPS) and our recently developed reaction coordinate identification methodology to investigate if such fast motions couple to the reaction in DHFR on the barrier-crossing timescale. While we identified some protein motions near the barrier crossing event, these motions do not constitute a compressive promoting vibration, and do not appear as a clearly identifiable protein component in reaction.

Original languageEnglish (US)
Pages (from-to)531-536
Number of pages6
JournalMolecular Physics
Issue number9-10
StatePublished - May 10 2012


  • TPS
  • enzymatic catalysis
  • kernel PCA
  • protein dynamics
  • reaction coordinate

ASJC Scopus subject areas

  • Biophysics
  • Molecular Biology
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry


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