TY - JOUR
T1 - Semiempirical QM/MM potential with simple valence bond (SVB) for enzyme reactions. Application to the nucleophilic addition reaction in haloalkane dehalogenase
AU - Devi-Kesavan, Lakshmi S.
AU - Garcia-Viloca, M.
AU - Gao, Jiali
PY - 2003/4/1
Y1 - 2003/4/1
N2 - 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.
AB - 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.
KW - Combined QM/MM
KW - Haloalkane dehalogenase
KW - Simple valence bond
UR - http://www.scopus.com/inward/record.url?scp=0038394700&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038394700&partnerID=8YFLogxK
U2 - 10.1007/s00214-002-0419-x
DO - 10.1007/s00214-002-0419-x
M3 - Article
AN - SCOPUS:0038394700
SN - 1432-881X
VL - 109
SP - 133
EP - 139
JO - Theoretical Chemistry Accounts
JF - Theoretical Chemistry Accounts
IS - 3
ER -