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Theoretical modeling of the control of reduction potential of heme in cytochrome c peroxidase
REDOX THERMODYNAMICS
A022
THEORETICAL MODELING OF THE CONTROL OF REDUCTION POTENTIAL HEME IN CYTOCHROME C PEROXIDASE
G. M Jensen (a), D. E. NcRee and A. Warshel (b)
(a),
D. 6. Goodin
29
OF
(a),
(a) Department of Molecular Biology, The Scripps Research Institute, 70666 N. Torrey Pines Road, La Jolla, CA 92037; (b) Department of Chemistry, University of Southern California, Los Angeles, CA 90089. In this work we evaluate the effect of the protein on the redox potential of the heme in cytochrome c peroxidase (CCP) using the PDLD (Protein Dipoles Langevin Dipoles) approach as implemented in the program POLARIS [ 1, 21 . The electrostatic interaction of a charged moiety - in this case, the heme - with its surroundings is expressed as the sum of four terms: VQm, VQa, VL and VB. VQm and VQa are respectively the interactions of the cluster with the partial charges and induced dipoles of protein atoms. VL and VB are interactions with solvent water, treated microscopically (as “Langevin dipoles”) within a sphere of radius rL, centered at the cluster, and macroscopically beyond. Langevin water dipoles are placed on a grid and oriented selfconsistently in the combined field from cluster charges, protein charges and induced dipoles and other water dipoles. Native and mutant CCP structures obtained by X-ray crystallography are utilized, as are structures generated by molecular dynamics. The theoretical data are correlated to electrochemical and spectroscopic data for native and mutant CCPs, including data providing information on heme ligand strength (3).
(1) R. Langen et al., J. Mo/.Biol. , 224, 589 (1992) (2) R. Langen et al., J. t3iol. Chem., 267, 25625 (1992) (3) D. B. Goodin and D. E. McRee, Biochemistry in press.
A022
THEORETICAL MODELING OF THE CONTROL OF REDUCTION POTENTIAL HEME IN CYTOCHROME C PEROXIDASE
G. M Jensen (a), D. E. NcRee and A. Warshel (b)
(a),
D. 6. Goodin
29
OF
(a),
(a) Department of Molecular Biology, The Scripps Research Institute, 70666 N. Torrey Pines Road, La Jolla, CA 92037; (b) Department of Chemistry, University of Southern California, Los Angeles, CA 90089. In this work we evaluate the effect of the protein on the redox potential of the heme in cytochrome c peroxidase (CCP) using the PDLD (Protein Dipoles Langevin Dipoles) approach as implemented in the program POLARIS [ 1, 21 . The electrostatic interaction of a charged moiety - in this case, the heme - with its surroundings is expressed as the sum of four terms: VQm, VQa, VL and VB. VQm and VQa are respectively the interactions of the cluster with the partial charges and induced dipoles of protein atoms. VL and VB are interactions with solvent water, treated microscopically (as “Langevin dipoles”) within a sphere of radius rL, centered at the cluster, and macroscopically beyond. Langevin water dipoles are placed on a grid and oriented selfconsistently in the combined field from cluster charges, protein charges and induced dipoles and other water dipoles. Native and mutant CCP structures obtained by X-ray crystallography are utilized, as are structures generated by molecular dynamics. The theoretical data are correlated to electrochemical and spectroscopic data for native and mutant CCPs, including data providing information on heme ligand strength (3).
(1) R. Langen et al., J. Mo/.Biol. , 224, 589 (1992) (2) R. Langen et al., J. t3iol. Chem., 267, 25625 (1992) (3) D. B. Goodin and D. E. McRee, Biochemistry in press.