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Structural Chemistry

, Volume 15, Issue 5, pp 405–414 | Cite as

MM and QM/MM Modeling of Threonyl-tRNA Synthetase: Model Testing and Simulations

  • Jolanta Zurek
  • Anna L. Bowman
  • W. Andrzej Sokalski
  • Adrian J. Mulholland
Article

Abstract

Aminoacyl-tRNA synthetases are centrally important enzymes in protein synthesis. We have investigated threonyl-tRNA synthetase from E. coli, complexed with reactants, using molecular mechanics and combined quantum mechanical/molecular mechanical (QM/MM) techniques. These modeling methods have the potential to provide molecular level understanding of enzyme catalytic processes. Modeling of this enzyme presents a number of challenges. The procedure of system preparation and testing is described in detail. For example, the number of metal ions at the active site, and their positions, were investigated. Molecular dynamics simulations suggest that the system is most stable when it contains only one magnesium ion, and the zinc ion is removed. Two different QM/MM methods were tested in models based on the findings of MM molecular dynamics simulations. AM1/CHARMM calculations resulted in unrealistic structures for the phosphates in this system. This is apparently due to an error of AM1. PM3/CHARMM calculations proved to be more suitable for this enzyme system. These results will provide a useful basis for future modeling investigations of the enzyme mechanism and dynamics.

QM/MM aminoacyl-tRNA synthetase AM1 PM3 CHARMM 

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Copyright information

© Plenum Publishing Corporation 2004

Authors and Affiliations

  • Jolanta Zurek
    • 1
    • 2
  • Anna L. Bowman
    • 1
  • W. Andrzej Sokalski
  • Adrian J. Mulholland
    • 1
  1. 1.Centre for Computational Chemistry, School of ChemistryUniversity of BristolBristolUnited Kingdom
  2. 2.Institute of Physical and Theoretical Chemistry I-30Wroclaw University of TechnologyWroclawPoland

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