| 51. |
- Rydberg, Patrik, et al.
(författare)
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Quantum-mechanical studies of reactions performed by cytochrome P450 enzymes
- 2012
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Ingår i: Current Inorganic Chemistry. - 1877-9441. ; 2, s. 292-315
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Forskningsöversikt (refereegranskat)abstract
- We review density functional theory studies of various types of reactions performed by the cytochrome P450 family of enzymes. We describe the various reactions on equal footing with an emphasisis on models to predict sites of metabolism for an arbitrary molecule. The activation barriers range between 0 and 109 kJ/mol, depending more on the atoms surrounding the reactive site than on the type of reaction. Therefore, the intrinsic reactivity can rather well be predicted by simple chemical rules. However, for a full predictive model, the steric effects of the enzyme surrounding the heme group need also to be modeled, which often is harder.
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| 52. |
- Ryde, Ulf
(författare)
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A fundamental view of enthalpy-entropy compensation
- 2014
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Ingår i: MedChemComm. - : Royal Society of Chemistry (RSC). - 2040-2511. ; 5:9, s. 1324-1336
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, enthalpy-entropy compensation (EEC) during the association of two molecules is studied by minimising model systems with molecular mechanics (MM) or quantum mechanics (QM), calculating translational, rotational, and vibrational contributions to the enthalpy and entropy with standard statistical-mechanics methods, using the rigid-rotor harmonic-oscillator approach. We start with simple two-atom models, for which dispersion and electrostatics can be studied separately, showing that there is no fundamental difference between dispersion, electrostatics, or even covalent interactions. All three types of interactions give rise to EEC and a saturation of T Delta S as Delta H becomes strongly negative. Next, homologous series of complexes dominated either by dispersion or hydrogen bonds are studied. We see no qualitative difference between results obtained at the MM or QM level, and for all complexes except two very weak, EEC is observed, owing to the loss of translational and rotational entropy, typically counteracted by the vibrational entropy. Within homologous series, linear relations between T Delta S and Delta H with slopes of 0.1-1.7 are obtained with no clear difference between dispersive or hydrogen-bonded systems (but similar to 0.01 for ionic and covalent interactions). These relations often reflect the increasing size of the complexes coming from the translational and rotational entropies, but at least for the hydrogen-bonded complexes, it is significantly enhanced also by the vibrational entropy (which depends on the strength of the interaction). Thus, for homologous series of molecules with repeated interactions studied in vacuum, EEC is a rule. However, if water molecules are added, the relation is blurred and it can be predicted that for a real binding reaction in water solution, both enthalpy-entropy compensation and anti-compensation can be observed, depending on the detailed interaction of the two molecules with water before and after binding, further complicated by dynamic effects.
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| 53. |
- Ryde, Ulf
(författare)
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Arguments for a narrow species concept in Rubus sect. Corylifolii
- 2011
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Ingår i: Nordic Journal of Botany. - : Wiley. - 0107-055X. ; 29:6, s. 708-721
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Tidskriftsartikel (refereegranskat)abstract
- A detailed inventory of Rubus sect. Corylifolii from the province of Halland in southwestern Sweden has been performed and the chromosome number of all distinct taxa and deviating morphotypes has been determined using flow cytometry. Once putative hybrids between Corylifolii and R. caesius or R. idaeus are recognized, essentially all stands of Corylifolii in Halland can be satisfactorily identified, including six taxa with a restricted distribution. Two of the latter have been noticed before: R. sordirosanthus (H. Hyl.) Ryde, found in over 100 localities and R. cordatiformis (Neuman) Ryde (comb. nov.) in almost 80 localities, but only in restricted areas, 23 and 7 km across. The other four have even smaller distributions (16 km across) and occur only in 315 localities. Clearly, they are local species in the terminology of Weber. Such species are currently usually left undescribed, which in the case of Halland would mean that 25% of the Corylifolii would remain without a name. Such a restriction leads to a number of problems: chaos in botanical collections and provincial floras, wide-spread species potentially being overlooked, red-listing becoming problematic, changes in the occurrence of local species becoming impossible to follow over time, and the Corylifolii treated differently from other apomictic groups. This study shows that a proper description of all local Corylifolii species would solve these problems. It is also argued that by doing so, the total number of Swedish species would not become particularly large, still remaining much lower than in other apomictic genera, like Hieracium, Taraxacum and Ranunculus. Therefore, the four local species are here described as R. onsalaensis Ryde, R. rugulosus Ryde, R. polybracteatus Ryde and R. soendrumensis Ryde.
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| 54. |
- Ryde, Ulf, et al.
(författare)
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Does DFT-D estimate accurate energies for the binding of ligands to metal complexes?
- 2011
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9234 .- 1477-9226. ; 40:Online 19 Aug 2011, s. 11176-11183
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the homolytic dissociation of a methyl radical from a model of methyl cobalamin. For this reaction, density functional theory with an atom-pairwise dispersion correction (DFT-D) gives a dispersion contribution to the bond dissociation energy (BDE) of 22-51 kJ mol(-1) depending on the functional, i.e. much more than common estimates for the total dispersion interaction energy of the methyl group in typical solvents. We show that this large energy correction results from many rather small (0-2 kJ mol(-1)) interactions that arise between the ligand and the metal and the other ligands when a short metal-ligand bond is formed. The energy terms result mostly from atom pairs connected by two or three bonds, i.e. terms that normally are ignored or scaled down at the molecular mechanics level, and have large contributions from r(-8) terms. The added dispersion energy diminishes the variation in the calculated BDE observed among various generalised-gradient approximation (GGA) functionals, whereas a gap still persists between the results of GGA and hybrid functionals. Model calculations at the local MP2 and CCSD (second-order perturbation theory and coupled cluster theory with single and double excitations) levels are in a similar range as the dispersion interactions estimated by DFT-D (23-29 kJ mol(-1)). However, both the DFT-D and the wavefunction-based results include middle-range correlation effects that vary greatly between different DFT methods owing to their different density-based description in the short-range regime. Therefore, it is not meaningful to discuss which DFT method gives the most accurate estimate of the dispersion contribution to the BDE. Moreover, for a balanced treatment of dispersion during the binding reaction in solution, the dispersion energy of the ligand and the unbound complex with the surroundings needs also to be considered, which decreases the net dispersion contribution to binding by ~20 kJ mol(-1).
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| 55. |
- Ryde, Ulf
(författare)
-
Genetic analysis shows that Rubus vikensis is a distinct species with a disjunct distribution
- 2010
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Ingår i: Nordic Journal of Botany. - : Wiley. - 0107-055X .- 1756-1051. ; 28:2, s. 246-250
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Tidskriftsartikel (refereegranskat)abstract
- Rubus vikensis A. Pedersen ex G. Wendt (sect. Corylifolii) was recently described from a restricted area in north western Scania, Sweden. In this investigation, I show that the same species occurs also on the Onsala peninsula in northern Halland and on a single locality in the middle of Halland. It has 35 chromosomes in all parts of the distribution area. Moreover, I show by random amplified polymorphic DNA (RAPD) analysis that R. vikensis is a distinct and well-defined species, clearly separated from the morphologically similar R. wahlbergii, with which it shares the chromosome number.
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| 56. |
- Ryde, Ulf, et al.
(författare)
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Quantum refinement of [FeFe] hydrogenase indicates a dithiomethylamine ligand
- 2010
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 132:13, s. 4512-4512
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Tidskriftsartikel (refereegranskat)abstract
- The active site of the [FeFe] hydrogenases contains two Fe ions bound to one Cys ligand, three CO molecules, two CN(-) ions, and a dithiolate ligand. The nature of the last of these has been much discussed, and it has been suggested that it contains C, N, or O as the bridgehead atom. Most experimental studies indicate a N atom, whereas a recent density functional theory (DFT) study of a crystal structure indicated an O atom. Here, we performed quantum refinement on the same crystal structure with five different models of the dithiolate ligand X(CH(2)S(-))(2), with X = CH(2), NH(2)(+), NH (two conformations), or O; we found that structures with a N bridgehead atom actually provide the best fit to the raw crystallographic data. Quantum refinement is standard crystallographic refinement in which the molecular mechanics force field normally used to supplement the experimental raw data to give a more chemical structure is replaced by more accurate DFT calculations for the active site. Thereby, we obtain structures that are an ideal compromise between DFT and crystallography.
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| 57. |
- Ryde, Ulf, et al.
(författare)
-
Rubus sordirosanthus in Halland, southwest Sweden
- 2010
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Ingår i: Svensk Botanisk Tidskrift. - 0039-646X. ; 104, s. 405-413
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in UndeterminedRubus sordirosanthus (sect. Corylifolii Lindl.) was published, although invalidly, by Hylander 1958 from the province of Halland, south-western Sweden. A holotype is here provided to make the name validly published. Recent field studies have shown that it occurs at almost 100 localities in a restricted area of c. 6 km around Steninge in central Halland. In addition, it is found on a former refuse tip in the city of Halmstad, 23 km to the south. A morpho- logically similar form has been found in three places at roadsides around the city of Varberg, 33 km to the north.We have used genetic methods to investigatethe relation between these forms and the related species R. wahlbergii Arrh. The chromosome num- ber of R. sordirosanthus from Steninge and Halmstad, as well as the Varberg form is 2n=28, in contrastto 2n=35 for R. wahlbergii. Moreover, RAPD DNA analysis shows that the two species are genetically separated. Rubus sordirosanthus from Steninge and Halmstad is homogeneous, whereas the Varberg form differs, although not in the direction towards R. wahlbergii. The latter species is genetically quite diverse. Thus, R. sordirosanthus is a well-defined and locally abundant species in Halland. On the other hand, the Varberg form gives the impression of being introduced in Varberg and therefore probably occurs also in other areas.Typification:Rubus sordirosanthus H. Hyl. ex Ryde nov. spec. Descr. orig.: H. Hylander, Botaniska Notiser 111, p. 521 (1958). Icon. (holotypus): Ibid. p. 522, fig. 3. Holotypus: Halland, Steninge bruk, Ö om Bräcketorp, ”ängen”, 13/7 1951. leg. H. Hylander (LD).
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| 58. |
- Shleev, Sergey, et al.
(författare)
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On the Possibility of Uphill Intramolecular Electron Transfer in Multicopper Oxidases: Electrochemical and Quantum Chemical Study of Bilirubin Oxidase
- 2012
-
Ingår i: Electroanalysis. - : Wiley. - 1040-0397 .- 1521-4109. ; 24:7, s. 1524-1540
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Tidskriftsartikel (refereegranskat)abstract
- The catalytic cycle of multicopper oxidases (MCOs) involves intramolecular electron transfer (IET) from the Cu-T1 copper ion, which is the primary site of the one-electron oxidations of the substrate, to the trinuclear copper cluster (TNC), which is the site of the four-electron reduction of dioxygen to water. In this study we report a detailed characterization of the kinetic and electrochemical properties of bilirubin oxidase (BOx) a member of the MCO family. The experimental results strongly indicate that under certain conditions, e.g. in alkaline solutions, the IET can be the rate-limiting step in the BOx catalytic cycle. The data also suggest that one of the catalytically relevant intermediates (most likely characterized by an intermediate oxidation state of the TNC) formed during the catalytic cycle of BOx has a redox potential close to 0.4 V, indicating an uphill IET process from the T1 copper site (0.7 V) to the Cu-T23. These suggestions are supported by calculations of the IET rate, based on the experimentally observed Gibbs free energy change and theoretical estimates of reorganization energy obtained by combined quantum and molecular mechanical (QM/MM) calculations.
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| 59. |
- Srnec, Martin, et al.
(författare)
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Reductive cleavage of the O-O bond in multicopper oxidases: a QM/MM and QM study
- 2011
-
Ingår i: Faraday Discussions. - : Royal Society of Chemistry (RSC). - 1364-5498. ; 148, s. 41-53
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Tidskriftsartikel (refereegranskat)abstract
- The key step in the reaction mechanism of multicopper oxidases (MCOs)-the cleavage of the O-O bond in O-2-has been investigated using combined quantum mechanical and molecular mechanical (QM/MM) methods. This process represents a reaction pathway from the peroxy intermediate after it accepts one electron from the nearby type-1 Cu site to the experimentally-observed native intermediate, which is the only fully oxidised catalytically relevant state in MCOs. Scans of the QM(DFT)/MM potential energy surface have allowed us to obtain estimates of the activation energies. Furthermore, vacuum calculations on a smaller model of the active site have allowed us to estimate the entropy contributions to the barrier height and to obtain further insight into the reaction by comparing the small cluster model with the QM/MM model, which includes the entire protein. Owing to the complicated electronic structure of these low-spin exchange coupled systems, multireference quantum chemical calculations at the complete-active space second-order perturbation theory (CASPT2) were used in an attempt to benchmark the barrier heights obtained at the DFT(B3LYP) level. Our best estimate of the activation barrier is Delta G = 60-65 kJ mol(-1), in good agreement with the experimental barrier of similar to 55 kJ mol(-1), which can be inferred from the experimental rate constant of k > 350 s(-1). It has also been shown that the reaction involves protonation of the O-2 moiety before bond cleavage. The proton likely comes from a nearby carboxylate residue which was recently suggested by the experiments.
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| 60. |
- Sumner, Sophie, et al.
(författare)
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Effect of geometry optimisations on QM-cluster and QM/MM studies of reaction energies in proteins
- 2013
-
Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 9:9, s. 4205-4214
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Tidskriftsartikel (refereegranskat)abstract
- We have examined the effect of geometry optimisation on energies calculated with the quantum-mechanical (QM) cluster, the combined QM and molecular-mechanics (QM/MM), the big-QM approaches (very large single-point QM calculations taken from QM/MM-optimised structures, including all atoms within 4.5 Å of the minimal active site, all buried charged groups in the protein, and truncations moved at least three residues away from the active site). We study a simple proton-transfer reaction between His-79 and Cys-546 in the active site of [Ni,Fe] hydrogenase and optimise QM systems of 50 different sizes (56–362 atoms). Geometries optimised with QM/MM are stable and reliable, whereas QM-cluster optimisations give larger changes in the structures and sometimes lead to large distortions in the active site if some hydrogen-bond partners to the metal ligands are omitted. Keeping 2–3 atoms for each truncated residue (rather than one) fixed in the optimisation improves the results, but does not solve all problems for the QM-cluster optimisations. QM-cluster energies in vacuum and a continuum solvent are insensitive to the geometry optimisations with a mean absolute change upon the optimisations of only 4–7 kJ/mol. This shows that geometry optimisations do not decrease the dependence of QM-cluster energies on how the QM system is selected – there is still a ~60 kJ/mol difference between calculations in which groups have been added to the QM system according to their distance to the active site or based on QM/MM free-energy components. QM/MM energies do not show such a difference, but they converge rather slowly with respect to the size of the QM system, although the convergence is improved by moving truncations away from the active site. The big-QM energies are stable over the 50 different optimised structures, 57±1 kJ/mol, although some smaller trends can be discerned. This shows that both QM-cluster geometries and energies should be interpreted with caution. Instead, we recommend QM/MM for geometry optimisations and energies calculated by the big-QM approach.
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