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A Computational Methodology to Screen Activities of Enzyme Variants

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  • Martin R Hediger
  • Luca De Vico
  • Allan Svendsen
  • Werner Besenmatter
  • Jan H Jensen

Abstract

We present a fast computational method to efficiently screen enzyme activity. In the presented method, the effect of mutations on the barrier height of an enzyme-catalysed reaction can be computed within 24 hours on roughly 10 processors. The methodology is based on the PM6 and MOZYME methods as implemented in MOPAC2009, and is tested on the first step of the amide hydrolysis reaction catalyzed by the Candida Antarctica lipase B (CalB) enzyme. The barrier heights are estimated using adiabatic mapping and shown to give barrier heights to within 3 kcal/mol of B3LYP/6-31G(d)//RHF/3-21G results for a small model system. Relatively strict convergence criteria (0.5 kcal/(molÅ)), long NDDO cutoff distances within the MOZYME method (15 Å) and single point evaluations using conventional PM6 are needed for reliable results. The generation of mutant structures and subsequent setup of the semiempirical calculations are automated so that the effect on barrier heights can be estimated for hundreds of mutants in a matter of weeks using high performance computing.

Suggested Citation

  • Martin R Hediger & Luca De Vico & Allan Svendsen & Werner Besenmatter & Jan H Jensen, 2012. "A Computational Methodology to Screen Activities of Enzyme Variants," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-10, December.
    • Handle: RePEc:plo:pone00:0049849
    DOI: 10.1371/journal.pone.0049849
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    Cited by:

    1. Shohreh Ariaeenejad & Maryam Mousivand & Parinaz Moradi Dezfouli & Maryam Hashemi & Kaveh Kavousi & Ghasem Hosseini Salekdeh, 2018. "A computational method for prediction of xylanase enzymes activity in strains of Bacillus subtilis based on pseudo amino acid composition features," PLOS ONE, Public Library of Science, vol. 13(10), pages 1-16, October.

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