Calibration of DFT Functionals for the Prediction of <sup>57</sup>Fe Mössbauer Spectral Parameters in Iron–Nitrosyl and Iron–Sulfur Complexes: Accurate Geometries Prove Essential

Sandala, Gregory M.; Hopmann, Kathrin H.; Ghosh, Abhik; Noodleman, Louis

doi:10.1021/ct200187d

Cited by 72 publications

(108 citation statements)

References 80 publications

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“…64,66,95−99 In practice, obtaining a value for ρ(0) for a given BS state requires a single-point energy calculation that employs a basis set that includes core electrons and that uses a higher value for the integration accuracy parameter than what is used in the geometry optimizations (i.e., 5.5 versus 4.0). 46 With the hypers2003 program, 100 ρ(0) can then be obtained from the ADF calculation.…”

Section: Methodsmentioning

confidence: 99%

Use of Broken-Symmetry Density Functional Theory To Characterize the IspH Oxidized State: Implications for IspH Mechanism and Inhibition

Blachly

Sandala

Giammona

et al. 2014

J. Chem. Theory Comput.

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With current therapies becoming less efficacious due to increased drug resistance, new inhibitors of both bacterial and malarial targets are desperately needed. The recently discovered methylerythritol phosphate (MEP) pathway for isoprenoid synthesis provides novel targets for the development of such drugs. Particular attention has focused on the IspH protein, the final enzyme in the MEP pathway, which uses its [4Fe–4S] cluster to catalyze the formation of the isoprenoid precursors IPP and DMAPP from HMBPP. IspH catalysis is achieved via a 2e–/2H+ reductive dehydroxylation of HMBPP; the mechanism by which catalysis is achieved, however, is highly controversial. The work presented herein provides the first step in assessing different routes to catalysis by using computational methods. By performing broken-symmetry density functional theory (BS–DFT) calculations that employ both the conductor-like screening solvation model (DFT/COSMO) and a finite-difference Poisson–Boltzmann self-consistent reaction field methodology (DFT/SCRF), we evaluate geometries, energies, and Mössbauer signatures of the different protonation states that may exist in the oxidized state of the IspH catalytic cycle. From DFT/SCRF computations performed on the oxidized state, we find a state where the substrate, HMBPP, coordinates the apical iron in the [4Fe–4S] cluster as an alcohol group (ROH) to be one of two, isoenergetic, lowest-energy states. In this state, the HMBPP pyrophosphate moiety and an adjacent glutamate residue (E126) are both fully deprotonated, making the active site highly anionic. Our findings that this low-energy state also matches the experimental geometry of the active site and that its computed isomer shifts agree with experiment validate the use of the DFT/SCRF method to assess relative energies along the IspH reaction pathway. Additional studies of IspH catalytic intermediates are currently being pursued.

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Section: Methodsmentioning

confidence: 99%

Use of Broken-Symmetry Density Functional Theory To Characterize the IspH Oxidized State: Implications for IspH Mechanism and Inhibition

Blachly

Sandala

Giammona

et al. 2014

J. Chem. Theory Comput.

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“…[32] In a more general sense, validation against experimental spectroscopic data has also been used to provide general benchmarks of computed Mössbauer data. [33,34] Beyond the UV/Vis/near-IR electronic transitions, the IR/Raman-based vibrational spectra, and the EPR and Mössbauer data, theoretical developments have turned to new spectroscopic approaches.…”

Section: Density Functional Theory Calculations Of Spectroscopic Propmentioning

confidence: 99%

Mono- and binuclear non-heme iron chemistry from a theoretical perspective

et al. 2016

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In this minireview, we provide an account of the current state-of-the-art developments in the area of mono-and binuclear non-heme enzymes (NHFe and NHFe2) and the smaller NHFe(2) synthetic models, mostly from a theoretical and computational perspective. The sheer complexity, and at the same time the beauty, of the NHFe(2) world represent a challenge for both experimental as well as theoretical methods. We emphasize that the concerted progress on both theoretical and experimental side is a conditio sine qua non for future understanding, exploration and utilization of the NHFe(2) systems.After briefly discussing the current challenges and advances in the computational methodology, we review the recent spectroscopic and computational studies of NHFe(2) enzymatic and inorganic systems and highlight the correlations between various experimental data (spectroscopic, kinetic, thermodynamic, electrochemical) and computations. Throughout, we attempt to keep in mind the most fascinating and attractive phenomenon in the NHFe(2) chemistry which is the fact that despite the strong oxidative power of many reactive intermediates, the NHFe(2) enzymes perform catalysis with high selectivity. We conclude with our personal viewpoint and hope that further developments in quantum chemistry and especially in the field of multireference wave function methods are needed to have a solid theoretical basis for the NHFe(2) studies, mostly by providing benchmarking and calibration of the computationally efficient and easy-to-use DFT methods.

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“…Such distortion can be further measured by Mossbauer spectroscopy (Pandelia, Lanz, Booker, & Krebs, 2015) and XAS (Einsle, Andrade, Dobbek, Meyer, & Rees, 2007; Ha et al, 2017) to evaluate the coordination geometry, solvation, and redox states of [Fe–S] clusters. These data can then be tested by computational modeling to investigate the electronic structures of the [Fe–S] clusters (Fee et al, 2003; Sandala, Hopmann, Ghosh, & Noodleman, 2011; Shomura, Yoon, Nishihara, & Higuchi, 2011). …”

Section: [Fe–s] Protein Crystallization Data Collection and Strumentioning

confidence: 99%

Robust Production, Crystallization, Structure Determination, and Analysis of [Fe–S] Proteins: Uncovering Control of Electron Shuttling and Gating in the Respiratory Metabolism of Molybdopterin Guanine Dinucleotide Enzymes

Tsai

Tainer

2018

Methods in Enzymology

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[Fe–S] clusters are essential cofactors in all domains of life. They play many biological roles due to their unique abilities for electron transfer and conformational control. Yet, producing and analyzing Fe–S proteins can be difficult and even misleading if not done anaerobically. Due to unique redox properties of [Fe–S] clusters and their oxygen sensitivity, they pose multiple challenges and can lose enzymatic activity or cause their component proteins to be structurally disordered due to [Fe–S] cluster oxidation and loss in air. Here we highlight tested protocols and strategies enabling efficient and stable [Fe–S] protein production, purification, crystallization, X-ray diffraction data collection, and structure determination. From multiple high-resolution anaerobic crystal structures, we furthermore analyze exemplary data defining [Fe–S] clusters, substrate entry, and product exit for the functional oxidation states of type II molybdo-bis(-molybdopterin guanine dinucleotide) (Mo-bisMGD) enzymes. Notably, these enzymes perform electron shuttling between quinone pools and specific substrates to catalyze respiratory metabolism. The identified structure–activity relationships for this enzyme class have broad implications germane to perchlorate environments on Earth and Mars extending to an alternative mechanism underlying metabolic origins for the evolution of the oxygen atmosphere. Integrated structural analyses of type II Mo-bisMGD enzymes unveil novel distinctive shared molecular mechanisms for dynamic control of substrate entry and product release gated by hydrophobic residues. Collective findings support a prototypic model for type II Mo-bisMGD enzymes including insights for a fundamental molecular mechanistic understanding of selectivity and regulation by a con-formationally gated channel with general implications for [Fe–S] cluster respiratory enzymes.

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Calibration of DFT Functionals for the Prediction of ⁵⁷Fe Mössbauer Spectral Parameters in Iron–Nitrosyl and Iron–Sulfur Complexes: Accurate Geometries Prove Essential

Cited by 72 publications

References 80 publications

Use of Broken-Symmetry Density Functional Theory To Characterize the IspH Oxidized State: Implications for IspH Mechanism and Inhibition

Use of Broken-Symmetry Density Functional Theory To Characterize the IspH Oxidized State: Implications for IspH Mechanism and Inhibition

Mono- and binuclear non-heme iron chemistry from a theoretical perspective

Robust Production, Crystallization, Structure Determination, and Analysis of [Fe–S] Proteins: Uncovering Control of Electron Shuttling and Gating in the Respiratory Metabolism of Molybdopterin Guanine Dinucleotide Enzymes

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Calibration of DFT Functionals for the Prediction of 57Fe Mössbauer Spectral Parameters in Iron–Nitrosyl and Iron–Sulfur Complexes: Accurate Geometries Prove Essential

Cited by 72 publications

References 80 publications

Use of Broken-Symmetry Density Functional Theory To Characterize the IspH Oxidized State: Implications for IspH Mechanism and Inhibition

Use of Broken-Symmetry Density Functional Theory To Characterize the IspH Oxidized State: Implications for IspH Mechanism and Inhibition

Mono- and binuclear non-heme iron chemistry from a theoretical perspective

Robust Production, Crystallization, Structure Determination, and Analysis of [Fe–S] Proteins: Uncovering Control of Electron Shuttling and Gating in the Respiratory Metabolism of Molybdopterin Guanine Dinucleotide Enzymes

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Calibration of DFT Functionals for the Prediction of ⁵⁷Fe Mössbauer Spectral Parameters in Iron–Nitrosyl and Iron–Sulfur Complexes: Accurate Geometries Prove Essential