31 research outputs found
Multiscale Modelling of Lytic Polysaccharide Monooxygenases
Lytic polysaccharide monooxygenase (LPMO) enzymes have attracted considerable
attention due to their ability to enhance polysaccharide depolymerization,
making them interesting in respect to production of biofuel from cellulose. The
LPMOs are metalloenzymes that contain a mononuclear copper active site that can
active dioxygen. However, many details of this activation are unclear, and have
previously been investigated from a computational angle. Yet, these studies
have either employed only molecular mechanics (MM), which are inaccurate for
metal active sites, or they have described only the active site with quantum
mechanics (QM) and neglected the effect of the protein. Here, we employ hybrid
QM and MM (QM/MM) methods to investigate the first steps of the LPMO mechanism,
which is reduction of of Cu(II) to Cu(I) and formation of a Cu(II)-superoxide
complex. In the latter complex, the superoxide can bind either in an equatorial
or an axial position. For both steps we obtain structures that are markedly
different from previous suggestions, based on vacuum calculations. Our
calculations show that the equatorial isomer of the superoxide complex is over
60 kJ/mol more stable than the axial isomer, being stabilized by interactions
with a second-coordination-sphere Gln residue, showing a possible role for this
residue. Coordination of superoxide in this manner is in agreement with recent
experimental suggestions.Comment: 21 pages, 6 figures, 3 tables. 20 pages Supporting Informatio
Molecular mechanism of lytic polysaccharide monooxygenases
The lytic polysaccharide monooxygenases (LPMOs) are copper metalloenzymes
that can enhance polysaccharide depolymerization through an oxidative mechanism
and hence boost generation of biofuel from e.g. cellulose. By employing density
functional theory in a combination of quantum mechanics and molecular mechanics
(QM/MM), we report a complete description of the molecular mechanism of LPMOs.
The QM/MM scheme allows us to describe all reaction steps with a detailed
protein environment and we show that this is necessary. Several active species
capable of abstracting a hydrogen from the substrate have been proposed
previously. We investigate previously suggested paths as well as new ones. We
describe the generation of the reactive intermediates, the abstraction of a
hydrogen atom from the polysaccharide substrate, as well as the final
recombination step in which OH is transferred back to the substrate. We show
that a superoxo [CuO2]+ complex can be protonated by a nearby histidine residue
(suggested by recent mutagenesis studies and crystallographic work) and,
provided an electron source is available, leads to formation of an oxyl-complex
after cleavage of the O-O bond and dissociation of water. The oxyl complex
either reacts with the substrate or is further protonated to a hydroxyl
complex. Both the oxyl and hydroxyl complexes are also readily generated from a
reaction with H2O2. The C-H abstraction by the oxyl and hydroxy complexes is
overall favorable with activation barriers of 69 and 94 kJ/mol, compared to the
much higher barrier (156 kJ/mol) obtained for the copper-superoxo species. We
obtain good structural agreement for intermediates for which structural data
are available and the estimated reaction energies agree with experimental rate
constants. Thus, our suggested mechanism is the most complete to date and
concur with available experimental evidence.Comment: Comments added + a few additional calculations after revision for
Chem. Sc
Exploration of H2 binding to the [NiFe]-hydrogenase active site with multiconfigurational density functional theory
The combination of density functional theory (DFT) with a
multiconfigurational wave function is an efficient way to include dynamical
correlation in calculations with multiconfiguration self-consistent field wave
functions. These methods can potentially be employed to elucidate reaction
mechanisms in bio-inorganic chemistry, where many other methods become either
too computationally expensive or too inaccurate. In this paper, a complete
active space (CAS) short-range DFT (CAS-srDFT) hybrid was employed to
investigate a bio-inorganic system, namely H2 binding to the active site of
[NiFe] hydrogenase. This system was previously investigated with
coupled-cluster (CC) and multiconfigurational methods in form of
cumulant-approximated second-order perturbation theory, based on the density
matrix renormalization group (DMRG). We find that it is more favorable for H2
to bind to Ni than to Fe, in agreement with previous CC and DMRG calculations.
The accuracy of CAS-srDFT is comparable to both CC and DMRG, despite that much
smaller active spaces were employed. This enhanced efficiency at smaller active
spaces shows that CAS-srDFT can become a useful method for bio-inorganic
chemistry.Comment: 22 page
Polarizable Embedding Based on Multiconfigurational Methods: Current Developments and the Road Ahead
Is density functional theory accurate for lytic polysaccharide monooxygenase enzymes?
The lytic polysaccharide monooxygenase (LPMO) enzymes boost polysaccharide
depolymerization through oxidative chemistry, which has fueled the hope for
more energy-efficient production of biofuel. We have recently proposed a
mechanism for the oxidation of the polysaccharide substrate (Hedeg{\aa}rd &
Ryde, Chem. Sci. 2018, 9, 3866). In this mechanism, complexes with superoxide,
oxyl, as well as hydroxyl (i.e. [CuO2]+, [CuO]+ and [CuOH]2+) cores were
involved. These complexes can have both singlet and triplet spin states, and
both spin-states may be important for how LPMOs function during catalytic
turnover. Previous calculations on LPMOs have exclusively been based on density
functional theory (DFT). However, different DFT functionals are known to
display large differences for spin-state splittings in transition-metal
complexes, and this has also been an issue for LPMOs. In this paper, we study
the accuracy of DFT for spin-state splittings in superoxide, oxyl, and hydroxyl
intermediates involved in LPMO turnover. As reference we employ
multiconfigurational perturbation theory (CASPT2).Comment: 29 pages, 5 figures, 5 table
Polarizable embedding with a multiconfiguration short-range density functional theory linear response method
We present here the coupling of a polarizable embedding (PE) model to the recently developed multiconfiguration short-range density functional theory method (MC-srDFT), which can treat multiconfigurational systems with a simultaneous account for dynamical and static correlation effects. PE-MC-srDFT is designed to combine efficient treatment of complicated electronic structures with inclusion of effects from the surrounding environment. The environmental effects encompass classical electrostatic interactions as well as polarization of both the quantum region and the environment. Using response theory, molecular properties such as excitation energies and oscillator strengths can be obtained. The PE-MC-srDFT method and the additional terms required for linear response have been implemented in a development version of DALTON. To benchmark the PE-MC-srDFT approach against the literature data, we have investigated the low-lying electronic excitations of acetone and uracil, both immersed in water solution. The PE-MC-srDFT results are consistent and accurate, both in terms of the calculated solvent shift and, unlike regular PE-MCSCF, also with respect to the individual absolute excitation energies. To demonstrate the capabilities of PE-MC-srDFT, we also investigated the retinylidene Schiff base chromophore embedded in the channelrhodopsin protein. While using a much more compact reference wave function in terms of active space, our PE-MC-srDFT approach yields excitation energies comparable in quality to CASSCF/CASPT2 benchmarks. (C) 2015 AIP Publishing LLC
Polarizable Embedding Complex Polarization Propagator in Four- and Two-Component Frameworks
Explicit embedding methods combined with the complex polarization propagator (CPP) enable the modeling of spectroscopy for increasingly complex systems with a high density of states. We present the first derivation and implementation of the CPP in four- and exact-two-component (X2C) polarizable embedding (PE) frameworks. We denote the developed methods PE-4c-CPP and PE-X2C-CPP, respectively. We illustrate the methods by estimating the solvent effect on ultraviolet-visible (UV-vis) and X-ray atomic absorption (XAS) spectra of [Rh(H2O)6]3+ and [Ir(H2O)6]3+ immersed in aqueous solution. We moreover estimate solvent effects on UV-vis spectra of a platinum complex that can be photochemically activated (in water) to kill cancer cells. Our results clearly show that the inclusion of the environment is required: UV-vis and (to a lesser degree) XAS spectra can become qualitatively different from vacuum calculations. Comparison of PE-4c-CPP and PE-X2C-CPP methods shows that X2C essentially reproduces the solvent effect obtained with the 4c methods