Molecular Modeling of Penicillin Acylase Binding with a Penicillin Nucleus by High Performance Computing: Can Enzyme or its Mutants Possess β-lactamase Activity?


  • Evgeny M. Kirilin Lomonosov Moscow State University, Moscow, Russia
  • Anna A. Bochkova Lomonosov Moscow State University, Belozersky Institute of Physicochemical Biology, Moscow, Russia
  • Nikolay V. Panin Lomonosov Moscow State University, Belozersky Institute of Physicochemical Biology, Moscow, Russia
  • Igor V. Pochinok Lomonosov Moscow State University, Research Computing Center, Moscow, Russia
  • Vytas Švedas Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow, Russia



moonlighting protein, penicillin acylase engineering, β-lactam antibiotics resistance, β-lactamase design, metadynamics


High-performance computing has been used for molecular modeling of penicillin acylase interaction with a penicillin nucleus 6-aminopenicillanic acid (6-APA) to assess whether the wild-type enzyme or its mutants could possess β-lactamase activity. Applying parallel hybrid GPU/CPU computing technologies for metadynamics calculations with the PLUMED library in conjunction with AMBER software suite it has been shown that trace amounts of wild-type penicillin acylase6-APA complexes leading to a β-lactamase reaction can be formed. Higher β-lactamase activity can be observed in enzyme mutants by introducing charged residue in the substrate binding pocket and its proper positioning with respect to a catalytic nucleophile, including stabilization of the tetrahedral intermediate in the oxyanion hole. Thus, it has been shown that the certain mutations facilitate the orientation of the substrate required for the manifestation of β-lactamase activity in the penicillin acylase active center.


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How to Cite

Kirilin, E. M., Bochkova, A. A., Panin, N. V., Pochinok, I. V., & Švedas, V. (2022). Molecular Modeling of Penicillin Acylase Binding with a Penicillin Nucleus by High Performance Computing: Can Enzyme or its Mutants Possess β-lactamase Activity?. Supercomputing Frontiers and Innovations, 9(2), 68–78.

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