TY - JOUR
T1 - QM/MM study of the product-enzyme complex in P450cam catalysis
AU - Lin, Hai
AU - Schöneboom, Jan C.
AU - Cohen, Shimrit
AU - Shaik, Sason
AU - Thiel, Walter
PY - 2004/7/15
Y1 - 2004/7/15
N2 - The enzyme-product complex in P450cam (CYP101) has been studied by combined quantum mechanical/molecular mechanical (QM/MM) calculations. The central iron(III) porphyrin complex and part of the catalytic product (5-exo-hydroxycamphor) are treated with density functional theory, while the protein/solvent environment is represented by the CHARMM force field. The computations indicate a doublet minimum at an Fe-O distance of ca. 2.2 Å, and a flat, barrierless potential for the dissociation of the Fe-O bond. Comparisons with analogous calculations on the isolated QM system in the gas phase show that inclusion of the protein/solvent environment lowers the activation energy for bond dissociation in the doublet state because of interactions within the binding pocket and accounts for a significant stabilization of the quartet and sextet states. The theoretical results allow for a tentative interpretation of recent ENDOR data (Davydov, R.; Makris, T. M. ; Kofman, V.; Werst, D. E.; Sligar, S. G.; Hoffman, B. M. J. Am. Chem. Soc. 2001, 123, 1403).
AB - The enzyme-product complex in P450cam (CYP101) has been studied by combined quantum mechanical/molecular mechanical (QM/MM) calculations. The central iron(III) porphyrin complex and part of the catalytic product (5-exo-hydroxycamphor) are treated with density functional theory, while the protein/solvent environment is represented by the CHARMM force field. The computations indicate a doublet minimum at an Fe-O distance of ca. 2.2 Å, and a flat, barrierless potential for the dissociation of the Fe-O bond. Comparisons with analogous calculations on the isolated QM system in the gas phase show that inclusion of the protein/solvent environment lowers the activation energy for bond dissociation in the doublet state because of interactions within the binding pocket and accounts for a significant stabilization of the quartet and sextet states. The theoretical results allow for a tentative interpretation of recent ENDOR data (Davydov, R.; Makris, T. M. ; Kofman, V.; Werst, D. E.; Sligar, S. G.; Hoffman, B. M. J. Am. Chem. Soc. 2001, 123, 1403).
UR - http://www.scopus.com/inward/record.url?scp=3442900466&partnerID=8YFLogxK
U2 - 10.1021/jp0493632
DO - 10.1021/jp0493632
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:3442900466
SN - 1520-6106
VL - 108
SP - 10083
EP - 10088
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 28
ER -