Journal ArticleDOI
Quantum Mechanical/Molecular Mechanical Study on the Mechanisms of Compound I Formation in the Catalytic Cycle of Chloroperoxidase: An Overview on Heme Enzymes
TLDR
This study enables us to generalize the mechanisms of O-O activation, elucidated so far by QM/MM calculations, for other heme enzymes, e.g., cytochrome P450cam, horseradish peroxidase (HRP), nitric oxide synthase (NOS), and heme oxygenase (HO).Abstract:
The formation of Compound I (Cpd I), the active species of the enzyme chloroperoxidase (CPO), was studied using QM/MM calculation. Starting from the substrate complex with hydrogen peroxide, FeIII−HOOH, we examined two alternative mechanisms on the three lowest spin-state surfaces. The calculations showed that the preferred pathway involves heterolytic O−O cleavage that proceeds via the iron hydroperoxide species, i.e., Compound 0 (Cpd 0), on the doublet-state surface. This process is effectively concerted, with a barrier of 12.4 kcal/mol, and is catalyzed by protonation of the distal OH group of Cpd 0. By comparison, the path that involves a direct O−O cleavage from FeIII−HOOH is less favored. A proton coupled electron transfer (PCET) feature was found to play an important role in the mechanism nascent from Cpd 0. Initially, the O−O cleavage progresses in a homolytic sense, but as soon as the proton is transferred to the distal OH, it triggers an electron transfer from the heme-oxo moiety to form water a...read more
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Density functional theory for transition metals and transition metal chemistry
TL;DR: In this article, the authors introduce density functional theory and review recent progress in its application to transition metal chemistry, including local, meta, hybrid, hybrid meta, and range-separated functionals, band theory, software, validation tests, and applications to spin states, magnetic exchange coupling, spectra, structure, reactivity, and solids.
Journal ArticleDOI
P450 Enzymes: Their Structure, Reactivity, and Selectivity—Modeled by QM/MM Calculations
TL;DR: This work confirms that setup issues can be resolved in a consistent manner if proper care is exercised and generates a common setup that gives QM/MM results for P450cam which are generally consistent with those obtained previously with individual setups.
Journal ArticleDOI
On the Role of Water in Peroxidase Catalysis: A Theoretical Investigation of HRP Compound I Formation
Pietro Vidossich,Giacomo Fiorin,Mercedes Alfonso-Prieto,Etienne Derat,Sason Shaik,Carme Rovira +5 more
TL;DR: This study provides an example of a system for which the "reactive configurations" correspond to a minor population of the system and shows how equilibrium molecular dynamics and free-energy calculations may conveniently be used to ascertain that such reactive conformations are indeed accessible to the system.
Journal ArticleDOI
Multireference and multiconfiguration ab initio methods in heme-related systems: what have we learned so far?
Hui Chen,Wenzhen Lai,Sason Shaik +2 more
TL;DR: This work reviews the recent applications of ab initio multireference/multiconfiguration (MR/MC) electronic structure methods to heme-related systems, involving tetra-, penta-, and hexa-coordinate species, as well as the high-valent iron-oxo species.
Journal ArticleDOI
ONIOM Study on a Missing Piece in Our Understanding of Heme Chemistry: Bacterial Tryptophan 2,3-Dioxygenase with Dual Oxidants
TL;DR: The involvement of dual oxidants, ferric-superoxide and ferryl-oxo (Cpd II) intermediates, is proposed to be responsible for the dioxygenase reactivity in bacterial TDO, and the not-well-recognized ferric -superoxide porphyrin intermediate is found to be capable of reacting with pi-systems via direct radical addition, an uncommon dioXYgen activation in the hemes.
References
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Journal ArticleDOI
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TL;DR: In this article, a semi-empirical exchange correlation functional with local spin density, gradient, and exact exchange terms was proposed. But this functional performed significantly better than previous functionals with gradient corrections only, and fits experimental atomization energies with an impressively small average absolute deviation of 2.4 kcal/mol.
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Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density
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Journal ArticleDOI
CHARMM: A program for macromolecular energy, minimization, and dynamics calculations
Bernard R. Brooks,Robert E. Bruccoleri,Barry D. Olafson,David J. States,S. Swaminathan,Martin Karplus +5 more
TL;DR: The CHARMM (Chemistry at Harvard Macromolecular Mechanics) as discussed by the authors is a computer program that uses empirical energy functions to model macromolescular systems, and it can read or model build structures, energy minimize them by first- or second-derivative techniques, perform a normal mode or molecular dynamics simulation, and analyze the structural, equilibrium, and dynamic properties determined in these calculations.
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A New Mixing of Hartree-Fock and Local Density-Functional Theories
TL;DR: In this article, a new coupling of Hartree-Fock theory with local density functional theory was proposed to improve the predictive power of the Hartree−Fock model for molecular bonding, and the results of tests on atomization energies, ionization potentials, and proton affinities were reported.