Solvent Entropy Contributions to Catalytic Activity in Designed and Optimized Kemp Eliminases

Saurabh Belsare, Viren Pattni, Matthias Heyden, Teresa Head-Gordon

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


We analyze the role of solvation for enzymatic catalysis in two distinct, artificially designed Kemp Eliminases, KE07 and KE70, and mutated variants that were optimized by laboratory directed evolution. Using a spatially resolved analysis of hydration patterns, intermolecular vibrations, and local solvent entropies, we identify distinct classes of hydration water and follow their changes upon substrate binding and transition state formation for the designed KE07 and KE70 enzymes and their evolved variants. We observe that differences in hydration of the enzymatic systems are concentrated in the active site and undergo significant changes during substrate recruitment. For KE07, directed evolution reduces variations in the hydration of the polar catalytic center upon substrate binding, preserving strong protein-water interactions, while the evolved enzyme variant of KE70 features a more hydrophobic reaction center for which the expulsion of low-entropy water molecules upon substrate binding is substantially enhanced. While our analysis indicates a system-dependent role of solvation for the substrate binding process, we identify more subtle changes in solvation for the transition state formation, which are less affected by directed evolution.

Original languageEnglish (US)
Pages (from-to)5300-5307
Number of pages8
JournalJournal of Physical Chemistry B
Issue number21
StatePublished - May 31 2018
Externally publishedYes

ASJC Scopus subject areas

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


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