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@ARTICLE{Zhao:857897,
      author       = {Zhao, Jing and Frauenkron-Machedjou, Victorine Josiane and
                      Fulton, Alexander and Zhu, Leilei and Davari, Mehdi D. and
                      Jaeger, Karl-Erich and Schwaneberg, Ulrich and Bocola,
                      Marco},
      title        = {{U}nraveling the effects of amino acid substitutions
                      enhancing lipase resistance to an ionic liquid: a molecular
                      dynamics study},
      journal      = {Physical chemistry, chemical physics},
      volume       = {20},
      number       = {14},
      issn         = {1463-9084},
      address      = {Cambridge},
      publisher    = {RSC Publ.66479},
      reportid     = {FZJ-2018-06851},
      pages        = {9600 - 9609},
      year         = {2018},
      abstract     = {Understanding of the structural and dynamic properties of
                      enzymes in non-aqueous media (e.g., ionic liquids, ILs) is
                      highly attractive for protein engineers and synthetic
                      biochemists. Despite a growing number of molecular dynamics
                      (MD) simulation studies on the influence of different ILs on
                      wild-type enzymes, the effects of various amino acid
                      substitutions on the stability and activity of enzymes in
                      ILs remain to be unraveled at the molecular level. Herein,
                      we selected fifty previously reported Bacillus subtilis
                      lipase A (BSLA) variants with increased resistance towards
                      an IL (15 $vol\%$ 1-butyl-3-methylimidazolium
                      trifluoromethanesulfonate; [Bmim][TfO]), and also ten
                      non-resistant BSLA variants for a MD simulation study to
                      identify the underlying molecular principles. Some important
                      properties differentiating resistant and non-resistant BSLA
                      variants from wild-type were elucidated. Results show that,
                      in 15 $vol\%$ [Bmim][TfO] aqueous solution, $40\%$ and
                      $60\%$ of non-resistant variants have lower and equal
                      probabilities to form a catalytically important hydrogen
                      bond between S77 and H156 compared to wild-type, whereas
                      $36\%$ and $56\%$ of resistant variants show increased and
                      equal probabilities, respectively. Introducing positively
                      charged amino acids close to the substrate-binding cleft for
                      instance I12R is beneficial for the BSLA resistance towards
                      15 $vol\%$ [Bmim][TfO], likely due to the reduced
                      probability of [Bmim]+ cations clustering near the cleft. In
                      contrast, substitution with a large hydrophobic residue like
                      I12F can block the cleft through hydrophobic interaction
                      with a neighboring nonpolar loop 134–137 or/and an
                      attractive π–π interaction with [Bmim]+ cations. In
                      addition, the resistant variants having polar substitutions
                      on the surface show higher ability to stabilize the surface
                      water molecule network in comparison to non-resistant
                      variants. This study can guide experimentalists to
                      rationally design promising IL–resistant enzymes, and
                      contribute to a deeper understanding of protein–IL
                      interactions at the molecular level.},
      cin          = {IMET / JARA-HPC},
      ddc          = {540},
      cid          = {I:(DE-Juel1)IMET-20090612 / $I:(DE-82)080012_20140620$},
      pnm          = {581 - Biotechnology (POF3-581) / Towards Discovery of
                      Molecular Determinants Underlying Organic Solvent Resistance
                      of Enzymes: Large- $(jara0169_20170501)$},
      pid          = {G:(DE-HGF)POF3-581 / $G:(DE-Juel1)jara0169_20170501$},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29578220},
      UT           = {WOS:000429205700059},
      doi          = {10.1039/C7CP08470F},
      url          = {https://juser.fz-juelich.de/record/857897},
}