A Computational Study of the Ionic Liquid-Induced Destabilization of the Miniprotein Trp-Cage

Betul Uralcan, Sang Beom Kim, Chester E. Markwalter, Robert K. Prud'Homme, Pablo G. Debenedetti

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Fundamental understanding of protein stability away from physiological conditions is important due to its evolutionary implications and relevance to industrial processing and storage of biological materials. The molecular mechanisms of stabilization/destabilization by environmental perturbations are incompletely understood. We use replica-exchange molecular dynamics simulations and thermodynamic analysis to investigate the effects of ionic liquid-induced perturbations on the folding/unfolding thermodynamics of the Trp-cage miniprotein. We find that ionic liquid-induced denaturation resembles cold unfolding, where the unfolded states are populated by compact, partially folded structures in which elements of the secondary structure are conserved, while the tertiary structure is disrupted. Our simulations show that the intrusion of ions and water into Trp-cage's hydrophobic core is facilitated by the disruption of its salt bridge and 310-helix by specific ion-residue interactions. Despite the swelling and widening of the hydrophobic core, however, Trp-cage's α-helix remains stable. We further show that ionic liquid disrupts protein-protein and protein-water hydrogen bonds while favoring the formation of ion-protein bonds, shifting the equilibrium of conformational states and promoting denaturation near room temperature.

Original languageEnglish (US)
Pages (from-to)5707-5715
Number of pages9
JournalJournal of Physical Chemistry B
Issue number21
StatePublished - May 31 2018

All Science Journal Classification (ASJC) codes

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


Dive into the research topics of 'A Computational Study of the Ionic Liquid-Induced Destabilization of the Miniprotein Trp-Cage'. Together they form a unique fingerprint.

Cite this