Challenges within the linear response approximation when studying enzyme catalysis and effects of mutations

J Chem Theory Comput. 2015 Jan 13;11(1):293-302. doi: 10.1021/ct500751f.


Various aspects of the linear response approximation (LRA) approach were examined when calculating reaction barriers within an enzyme and its different mutants. Scaling the electrostatic interactions is shown to slightly affect the absolute values of the barriers but not the overall trend when comparing wild-type and mutants. Convergence of the overall energetics was shown to depend on the sampling. Finally, the contribution of particular residues was shown to be significant, despite its small value.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemistry
  • Alcohols / metabolism
  • Biocatalysis*
  • Hydrocarbons, Halogenated / chemistry
  • Hydrocarbons, Halogenated / metabolism
  • Hydrolases / chemistry
  • Hydrolases / genetics*
  • Hydrolases / metabolism*
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Mutant Proteins / metabolism*
  • Mutation*
  • Quantum Theory
  • Static Electricity


  • Alcohols
  • Hydrocarbons, Halogenated
  • Mutant Proteins
  • Hydrolases
  • haloalkane dehalogenase