Vibrational softening of a protein on ligand binding

Erika Balog, David Perahia, Jeremy C. Smith, Franci Merzel

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Neutron scattering experiments have demonstrated that binding of the cancer drug methotrexate softens the low-frequency vibrations of its target protein, dihydrofolate reductase (DHFR). Here, this softening is fully reproduced using atomic detail normal-mode analysis. Decomposition of the vibrational density of states demonstrates that the largest contributions arise from structural elements of DHFR critical to stability and function. Mode-projection analysis reveals an increase of the breathing-like character of the affected vibrational modes consistent with the experimentally observed increased adiabatic compressibility of the protein on complexation.

Original languageEnglish
Pages (from-to)6811-6817
Number of pages7
JournalJournal of Physical Chemistry B
Volume115
Issue number21
DOIs
Publication statusPublished - Jun 2 2011

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ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

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