Computational Studies of Heme Proteins: P450s and Peroxidases

Theory and Physical Properties and Reactivity in P450s
(completed in January 2003)
NIH Danni L. Harris
Theory of Heme Proteins
(completed in September 2002)
NSF Danni L. Harris

Our group is studying several questions related to the structure, spectra and function of heme proteins. In particular, the role of proximal and distal heme binding site regions of heme proteins determine the mechanism of formation and nature of the active intermediates, enzymatic efficacy and control of oxidative/reductive chemistry at the heme binding site. Most recent research in P450s at MRI spans several areas including: 1) reaction pathway studies in cytochrome P450 monoxygenases, studies of an unusual P450 with reductase activity (P450nor), as well as new work investigating nitric oxide synthase employing DFT, INDO-ROHF-CI and molecular mechanics methods; 2) construction an assessment of new models of mammalian P450s CYP2E1, CYP1A2 and CYP2C9 based on a mammalian template of known structure, mutant rabbit CYP2C5.

Current research related to peroxidases entails the prediction of modes of binding, investigation of the mechanism of formation and specific products formed for ligands of horseradish (HRP) and chloroperoxidase (CPO) employing molecular dynamics, docking, and density functional theoretical studies.