Damien Laage's Group - EOS Project

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EOS Project: Enzyme Catalysis in Organic Solvents

EU FP7 ERC

ERC Starting Grant (Consolidator)

Project 279977

January 2012 - December 2016

Goal

Enzymes are remarkably efficient catalysts and their recent use in non-aqueous organic solvents is opening up a tremendous range of applications in synthetic chemistry: since, surprisingly, most enzymes do not denature in these non-natural environments, new reactions involving e.g. water-insoluble reagents can be catalyzed, while unwanted degradation side reactions are suppressed.

However, a key challenge for these applications is to overcome the greatly reduced catalytic activity compared to aqueous conditions. Empirically, adding activators such as salts or small amounts of water dramatically enhances the activity, but the underlying mechanisms have remained elusive, thus preventing a rational optimization.

Through analytic modeling and numerical simulations, our goal is to provide an atomic-scale detailed description of enzyme catalysis in organic solvents, including the key role of the environment. This molecular insight will then be used to design rigorous new procedures for the rational engineering of systems with dramatically enhanced activities, both through optimized choices of solvents and additives, and through targeted protein mutations.

Participants

Dr Damien Laage P.I.
Dr Kristen Marino Postdoctoral researcher (2012-2013)
Dr Dominik Domin Postdoctoral researcher (2013-2015)
Dr Kakali Sen Postdoctoral researcher (2013-2015)
Dr Eva Pluharova Postdoctoral researcher (2014-2016)
Dr Nicolas Chéron Postdoctoral researcher (2015-2017)
Ms Aoife Fogarty Graduate student (2012-2013)
Ms Elise Duboué-Dijon Graduate student (2012-2015)

Facilities

Dedicated high-performance computer cluster including more than 440 Intel Xeon cores, 70 Tb of disk space and QDR Infiniband connections.

Publications

  1. Aoife C. Fogarty, Elise Duboué-Dijon, Fabio Sterpone, James T. Hynes and Damien Laage, "Biomolecular hydration dynamics: a jump model perspective", Chem. Soc. Rev. 42, 5672-5683 (2013) (PDF)
  2. Guillaume Stirnemann, Erik Wernersson, Pavel Jungwirth and Damien Laage, "Mechanisms of acceleration and retardation of water dynamics by ions", J. Am. Chem. Soc. 135, 11824-11831 (2013) (PDF)
  3. Aoife C. Fogarty and Damien Laage, "Water Dynamics in Protein Hydration Shells: The Molecular Origins of the Dynamical Perturbation", J. Phys. Chem. B 118, 7715-7729 (2014) (PDF)
  4. Iñaki Tuñón, Damien Laage, James T. Hynes, "Are there dynamical effects in enzyme catalysis? Some thoughts concerning the enzymatic chemical step", Arch. Biochem. Biophys. 582, 42-55 (2015) (PDF)
  5. Elise Duboué-Dijon and Damien Laage, "Characterization of the Local Structure in Liquid Water by Various Order Parameters", J. Phys. Chem. B 119, 8406 (2015) (PDF)
  6. Eva Pluhařová, Nicolas Chéron and Damien Laage, "Effects of Water and Non-aqueous Solvents on Enzyme Activity", in "Simulating Enzyme Reactivity: Computational Methods in Enzyme Catalysis", I. Tuñón and V. Moliner Eds, RSC, London, 2017 (PDF)
  7. James T. Hynes, Damien Laage, Iñaki Tuñón, "A Transition-State Perspective for Enzymatic Reactions", in "Simulating Enzyme Reactivity: Computational Methods in Enzyme Catalysis", I. Tuñón and V. Moliner Eds, RSC, London, 2017
  8. Guillaume Stirnemann, Elise Duboué-Dijon, Damien Laage, "Ab Initio Simulations of water Dynamics in Aqueous TMAO Solutions: Temperature and Concentration Effects", J. Phys. Chem. B 121, 11189-11197 (2017) (PDF)
  9. Elise Duboué-Dijon, Eva Pluhařová, Dominik Domin, Kakali Sen, Aoife C. Fogarty, Nicolas Chéron, Damien Laage "Coupled Valence-Bond State Molecular Dynamics Description of an Enzyme-Catalyzed Reaction in a Non-Aqueous Organic Solvent", J. Phys. Chem. B 121, 7027-7041 (2017) (PDF)
  10. Damien Laage, Thomas Elsaesser, James T. Hynes, "Structure and ultrafast dynamics of biomolecular hydration shells", Struct. Dyn. 4, 044018 (2017) (PDF)
  11. Eva Pluhařová, Damien Laage, Pavel Jungwirth, "Size and Origins of Long-Range Orientational Water Correlations in Dilute Aqueous Salt Solutions", J. Phys. Chem. Lett. 8, 2031 (2017) (PDF)
  12. Damien Laage, Thomas Elsaesser, James T. Hynes, "Water Dynamics in the Hydration Shells of Biomolecules" Chem. Rev. 117, 10694 (2017) (PDF)