How the disulfide conformation determines the disulfide/thiol redox potential

Research output: Contribution to JournalArticleAcademicpeer-review


Protein disulfides can adopt a wide variety of conformations, each having different energies. Limited experimental data suggest that disulfides adopting a high energy have an enhanced likelihood for reduction, but the exact nature of this relation is not clear. Using a computational approach, we give insight on the conformational dependence of the redox behavior of the disulfide bond, which relates structure to reactivity. The relative energy of different conformations of the diethyl disulfide model system correlates with the disulfide/thiol redox potential E°. Insight in the calculated redox potentials is obtained via quantitative molecular orbital theory, and via the decomposition of E° into a vertical electron affinity and a subsequent reorganization term. We have identified the determinants of the disulfide conformational energies and characterized the barrier to rotation around the disulfide bond. Our findings on the diethyl disulfide model system can be transferred to examples from the Protein Data Base. In conclusion, strained disulfide conformations with a high conformational energy have a large tendency to be reduced. Upon reduction, unfavorable interactions are released. This explains why reorganization effects and not a higher tendency to accept electrons account for the high reduction potential of high-energy disulfides.
Original languageEnglish
Pages (from-to)93-103
Number of pages11
JournalJournal of Biomolecular Structure and Dynamics
Issue number1
Publication statusPublished - 2 Jan 2015


  • quantitative MO theory
  • structure-reactivity relations
  • disulfide/thiol redox potential
  • conformation
  • disulfide


Dive into the research topics of 'How the disulfide conformation determines the disulfide/thiol redox potential'. Together they form a unique fingerprint.

Cite this