Abstract.
We present a method for the correction of errors in combined QM/MM calculations using a semiempirical Hamiltonian for enzyme reactions. Since semiempirical models can provide a reasonable representation of the general shape of the potential energy surface for chemical reactions, we introduce a simple valence bond-like (SVB) term to correct the energies at critical points on the potential energy surface. The present SVB term is not a stand-alone potential energy function, but it is used purely for introducing small energy corrections to the semiempirical Hamiltonian to achieve the accuracy needed for modeling enzymatic reactions. We show that the present coupled QM-SVB/MM approach can be parameterized to reproduce experimental and ab initio results for model reactions, and have applied the PM3-SVB/MM potential to the nucleophilic addition reaction in haloalkane dehalogenase. In a preliminary energy minimization study, the PM3-SVB/MM results are reasonable, suggesting that it may be used in free energy simulations to assess enzymatic reaction mechanism.
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Received: 1 November 2001 / Accepted: 6 September 2002 / Published online: 19 February 2003
Contribution to the Proceedings of the Symposium on Combined QM/MM Methods at the 222nd National Meeting of the American Chemical Society, 2001
Correspondence to: Lakshmi S. Devi-Kesavan e-mail: kesavan@chem.umn.edu
Acknowledgments. The work is partially supported by the NIH and the NSF.
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Devi-Kesavan, L., Garcia-Viloca, M. & Gao, J. Semiempirical QM/MM potential with simple valence bond (SVB) for enzyme reactions. Application to the nucleophilic addition reaction in haloalkane dehalogenase. Theor Chem Acc 109, 133–139 (2003). https://doi.org/10.1007/s00214-002-0419-x
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DOI: https://doi.org/10.1007/s00214-002-0419-x