Journal Article

FZJ-2021-02979

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Aqueous ionic liquids redistribute local enzyme stability via long-range perturbation pathways

El Harrar, T.FZJ* ; Frieg, B.FZJ* ; Davari, M. D. ; Jaeger, K.-E.FZJ* ; Schwaneberg, U. ; Gohlke, H. (Corresponding author)FZJ*

2021
Research Network of Computational and Structural Biotechnology (RNCSB) Gotenburg

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Please use a persistent id in citations: http://hdl.handle.net/2128/28430  doi:10.1016/j.csbj.2021.07.001

Abstract: Ionic liquids (IL) and aqueous ionic liquids (aIL) are attractive (co-)solvents for biocatalysis due to their unique properties. On the other hand, the incubation of enzymes in IL or aIL often reduces enzyme activity. Recent studies proposed various aIL-induced effects to explain the reduction, classified as direct effects, e.g., local dehydration or competitive inhibition, and indirect effects, e.g., structural perturbations or disturbed catalytic site integrity. However, the molecular origin of indirect effects has largely remained elusive. Here we show by multi-μs long molecular dynamics simulations, free energy computations, and rigidity analyses that aIL favorably interact with specific residues of Bacillus subtilis Lipase A (BsLipA) and modify the local structural stability of this model enzyme by inducing long-range perturbations of noncovalent interactions. The perturbations percolate over neighboring residues and eventually affect the catalytic site and the buried protein core. Validation against a complete experimental site saturation mutagenesis library of BsLipA (3620 variants) reveals that the residues of the perturbation pathways are distinguished sequence positions where substitutions highly likely yield significantly improved residual activity. Our results demonstrate that identifying these perturbation pathways and specific IL ion-residue interactions there effectively predicts focused variant libraries with improved aIL tolerance.

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Contributing Institute(s):

1. Jülich Supercomputing Center (JSC)
2. Strukturbiochemie (IBI-7)
3. Institut für Molekulare Enzymtechnologie (HHUD) (IMET)
4. Bioinformatik (IBG-4)
5. John von Neumann - Institut für Computing (NIC)

Research Program(s):

1. 5111 - Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)
2. 2171 - Biological and environmental resources for sustainable use (POF4-217) (POF4-217)
3. Forschergruppe Gohlke (hkf7_20200501) (hkf7_20200501)
4. CSD-SSD - Center for Simulation and Data Science (CSD) - School for Simulation and Data Science (SSD) (CSD-SSD-20190612) (CSD-SSD-20190612)

Appears in the scientific report 2021

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Database coverage:
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