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Theoretical Chemistry Accounts

, Volume 109, Issue 3, pp 118–124 | Cite as

A charge-scaling method to treat solvent in QM/MM simulations

  • Aaron R. Dinner
  • Xabier Lopez
  • Martin Karplus
Regular article

Abstract.

 We present a method to treat the solvent efficiently in hybrid quantum mechanical/molecular mechanical simulations of chemical reactions in enzymes. The method is an adaptation of an approach developed for molecular-mechanical free-energy simulations. The charges of each of the exposed ionizable groups are scaled, and the system is simulated in the presence of a limited number of explicit solvent molecules to obtain a reasonable set of structures. Continuum electrostatics methods are then used to correct the energies. Variations in the procedure are discussed with an emphasis on modifications from the original protocol. We illustrate the method by applying it to the study of a hydrolysis reaction in a highly charged system comprising a complex between the base excision repair enzyme uracil-DNA glycosylase and double-stranded DNA. The resulting adiabatic reaction profile is in good agreement with experiment, in contrast to that obtained without scaling the charges.

Keywords: Uracil – DNA glycosylase – Hybrid quantum mechanical/molecular mechanical simulation methods – Solvent shielding – Poisson – Boltzmann continuum electrostatics 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • Aaron R. Dinner
    • 1
  • Xabier Lopez
    • 2
  • Martin Karplus
    • 3
  1. 1.Department of Chemistry, University of California, Berkeley, CA 94720, USA.US
  2. 2.Kimika Fakultatea, Euskal Herriko Unibertsitatea, P. K. 1072 20080 Donostia, SpainES
  3. 3.Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford St., Cambridge, MA 02138, USA.US

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