The European Physical Journal Special Topics

, Volume 227, Issue 14, pp 1631–1638 | Cite as

Molecular simulations of enzymes under non-natural conditions

  • Valerio Ferrario
  • Jürgen Pleiss
Regular Article
Part of the following topical collections:
  1. Particle Methods in Natural Science and Engineering


The development of novel sustainable biocatalytic processes requires systematic and comprehensive tools for engineering, integrated into a framework for the simultaneous optimization of enzyme, substrate, solvent, and reaction conditions. The experimentally determined biochemical properties of the biocatalyst are mediated by four interactions: between substrate and solvent, protein and solvent, protein and substrate, as well as protein–protein interactions. Molecular dynamics simulations were applied to study these interactions from first principles. The interaction of the substrate with the solvent was described by its activity coefficient, the interaction of the substrate with the protein and substrate access to the active site were characterized by a binding free energy along a reaction coordinate, and the protein–solvent interaction was modeled by a Langmuir model. The simulation of protein aggregation identified a delicate balance of kinetics and thermodynamics of competing contacts during the nucleation process.


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Copyright information

© EDP Sciences, Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of Biochemistry and Technical Biochemistry, University of StuttgartStuttgartGermany

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