| 1. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 2. |
- Bergmann, Justin, et al.
(författare)
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Can the results of quantum refinement be improved with a continuum-solvation model?
- 2021
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Ingår i: Acta Crystallographica. Section B: Structural Science. - 0108-7681. ; 77:6, s. 906-918
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Tidskriftsartikel (refereegranskat)abstract
- Quantum refinement has repeatedly been shown to be a powerful approach to interpret and improve macromolecular crystal structures, allowing for the discrimination between different interpretations of the structure, regarding the protonation states or the nature of bound ligands, for example. In this method, the empirical restraints, used to supplement the crystallographic raw data in standard crystallographic refinement, are replaced by more accurate quantum mechanical (QM) calculations for a small, but interesting, part of the structure. Previous studies have shown that the results of quantum refinement can be improved if the charge of the QM system is reduced by adding neutralizing groups. However, this significantly increases the computation time for the refinement. In this study, we show that a similar improvement can be obtained if the original highly charged QM system is instead immersed in a continuum solvent in the QM calculations. The best results are typically obtained with a high dielectric constant (ε). The continuum solvent improves real-space it Z values, electron-density difference maps and strain energies, and it normally does not affect the discriminatory power of the calculations between different chemical interpretations of the structure. However, for structures with a low charge in the QM system or with a low crystallographic resolution (>2Å), no improvement of the structures is seen.
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| 3. |
- Bergmann, Justin, et al.
(författare)
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Combining crystallography with quantum mechanics
- 2022
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Ingår i: Current Opinion in Structural Biology. - : Elsevier BV. - 0959-440X. ; 72, s. 18-26
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Forskningsöversikt (refereegranskat)abstract
- In standard crystallographic refinement of biomacromolecules, the crystallographic raw data are supplemented by empirical restraints that ensure that the structure makes chemical sense. These restraints are typically accurate for amino acids and nucleic acids, but less so for cofactors, substrates, inhibitors, ligands and metal sites. In quantum refinement, this potential is replaced by more accurate quantum mechanical (QM) calculations. Several implementations have been presented, differing in the level of QM and whether it is used for the entire structure or only for a site of particular interest. It has been shown that the method can improve and correct errors in crystal structures and that it can be used to determine protonation and tautomeric states of various ligands and to decide what is really seen in the structure by refining different interpretations and using standard crystallographic and QM quality measures to decide which fits the structure best.
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| 4. |
- Bergmann, Justin
(författare)
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Computational protein crystallography : How to get the most out of your data
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is important to obtain accurate three dimensional structures of molecules and proteins to understand and predict their function and behaviour. X-ray crystallography is the major technique to determine three dimensional structures of proteins. Although there have been major improvements on the experimental side in determining crystallographic data, only small progress has been made on the computational side to get a correct model andinterpretation of this data.In small-molecule crystallography, some of the shortcomings in the model have already been overcome, but in protein crystallography they still remain. Therefore, we have adapted the Hirshfeld atom refinement from small-molecule crystallography to make it available also to protein crystallography. This enables improved modelling of high-resolution protein data. To achieve this goal, we combined the molecular fractionation with conjugate caps approach with the Hirshfeld atom refinement. We call this combined method fragHAR. With fragHAR, we could perform the first Hirshfeld atom refinement of a metalloprotein.Furthermore, we improved and applied the quantum refinement method, which employs quantum mechanics calculations to obtain a chemically and physically correct model for all parts of the protein, especially the active site. With quantum refinement, it is possible to distinguish between different interpretations of the structure, e.g. the elemental composition or the protonation state, even from medium-resolution crystallographic data. In this thesis, quantum refinement was improved for highly-charged systems by applying a continuum-solvent description of the surroundings in the quantum mechanics calculation. Furthermore, quantum refinement was applied to settle the nature of the unusual bidentate ligand in V-nitrogenase and the protonation state of the MoFe cluster in Mo-nitrogenase when inhibited by CO. For a recent structure of Mo-nitrogenase, we showed that there is no experimental support for the suggestion that N 2 is bound to the MoFe-cluster and presented a more likely model. We have also identified the most probable protonation states of the active site in acetylcholinesterase before and after inhibition by nerve agents. Finally, for triosephosphate isomerase we used a joint X-ray and neutron quantum refinement to investigate the hydrogen bond between an inhibitor and Lys-13.
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| 5. |
- Bergmann, Justin, et al.
(författare)
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Critical evaluation of a crystal structure of nitrogenase with bound N2 ligands
- 2021
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Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 0949-8257 .- 1432-1327. ; 26:2-3, s. 341-353
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a 1.83 Å crystallographic structure of nitrogenase was suggested to show N2-derived ligands at three sites in the catalytic FeMo cluster, replacing the three μ2 bridging sulfide ligands (two in one subunit and the third in the other subunit) (Kang et al. in Science 368: 1381–1385, 2020). Naturally, such a structure is sensational, having strong bearings on the reaction mechanism of the enzyme. Therefore, it is highly important to ensure that the interpretation of the structure is correct. Here, we use standard crystallographic refinement and quantum refinement to evaluate the structure. We show that the original crystallographic raw data are strongly anisotropic, with a much lower resolution in certain directions than others. This, together with the questionable use of anisotropic B factors, give atoms an elongated shape, which may look like diatomic atoms. In terms of standard electron-density maps and real-space Z scores, a resting-state structure with no dissociated sulfide ligands fits the raw data better than the interpretation suggested by the crystallographers. The anomalous electron density at 7100 eV is weaker for the putative N2 ligands, but not lower than for several of the μ3 bridging sulfide ions and not lower than what can be expected from a statistical analysis of the densities. Therefore, we find no convincing evidence for any N2 binding to the FeMo cluster. Instead, a standard resting state without any dissociated ligands seems to be the most likely interpretation of the structure. Likewise, we find no support that the homocitrate ligand should show monodentate binding. Graphic abstract: [Figure not available: see fulltext.].
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| 6. |
- Bergmann, Justin, et al.
(författare)
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Quantum-refinement studies of the bidentate ligand of V‑nitrogenase and the protonation state of CO-inhibited Mo‑nitrogenase
- 2021
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 0162-0134. ; 219
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Tidskriftsartikel (refereegranskat)abstract
- Nitrogenase is the only enzyme that can cleave the triple bond in N2, making nitrogen available to plants (although the enzyme itself is strictly microbial). It has been studied extensively with both experimental and computational methods, but many details of the reaction mechanism are still unclear. X-ray crystallography is the main source of structural information for biomacromolecules, but it has problems to discern hydrogen atoms or to distinguish between elements with the same number of electrons. These problems can sometimes be alleviated by introducing quantum chemical calculations in the refinement, providing information about the ideal structure (in the same way as the empirical restraints used in standard crystallographic refinement) and comparing different interpretations of the structure with normal crystallographic and quantum mechanical quality measures. We have performed such quantum-refinement calculations to address two important issues for nitrogenase. First, we show that the bidentate ligand of the active-site FeV cluster in V‑nitrogenase is carbonate, rather than bicarbonate or nitrate. Second, we study the CO-inhibited structure of Mo‑nitrogenase. CO binds to a reduced and protonated state of the enzyme by replacing one of the sulfide ions (S2B) in the active-site FeMo cluster. We examined if it is possible to deduce from the crystal structure the location of the protons. Our results indicates that the crystal structure is best modelled as fully deprotonated.
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| 7. |
- Cao, Lili, et al.
(författare)
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Geometry and Electronic Structure of the P-Cluster in Nitrogenase Studied by Combined Quantum Mechanical and Molecular Mechanical Calculations and Quantum Refinement
- 2019
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 58:15, s. 9672-9690
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the geometry and electronic structure of the P-cluster in nitrogenase in four oxidation states: PN, P1+, P2+, and P3+. We have employed combined quantum mechanical and molecular mechanical (QM/MM) calculations, using two different density-functional theory methods, TPSS and B3LYP. The calculations confirm that the side chain of Ser-188 is most likely deprotonated in the partly oxidized P1+ state, thereby forming a bond to Fe6. Likewise, the backbone amide group of Cys-88 is deprotonated in the doubly oxidized P2+ state, forming a bond to Fe5. The calculations also confirm the two conformations of the P-cluster in the atomic-resolution crystal structure of the enzyme, representing the PN and P2+ states, but show that the finer differences between the two structures are not fully reflected in the crystal structure, because the coordinates of only two atoms differ between the two conformations. However, the recent crystal structure of the P1+ state seems to be of lower quality with many dubious Fe-Fe and Fe-S distances. Quantum refinement of this structure indicates that it is a mixture of the P1+ and P2+ states but confirms that the side chain of Ser-188 is most likely deprotonated in both states. TPSS gives structures that are appreciably closer to the crystal structures than does B3LYP. In addition, we have studied all 16-48 possible broken-symmetry states of the four oxidation states of the P-cluster with DFT in the one or two observed spin states. For the reduced PN state, we can settle the most likely state from the calculated energies and geometries. However, for the more oxidized states there are large differences in the predictions obtained with the two DFT methods.
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| 8. |
- Cirri, Damiano, et al.
(författare)
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Computationally enhanced X-ray diffraction analysis of a gold(III) complex interacting with the human telomeric DNA G-quadruplex. Unravelling non-unique ligand positioning
- 2022
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Ingår i: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130. ; 211, s. 506-513
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Tidskriftsartikel (refereegranskat)abstract
- The crystal structure of the human telomeric DNA Tel24 G-quadruplex (Tel24 = TAG3(T2AG3)3T) in complex with the novel [AuL] species (with L = 2,4,6-tris(2-pyrimidyl)-1,3,5-triazine - TPymT-α) was solved by a novel joint molecular mechanical (MM)/quantum mechanical (QM) innovative approach. The quantum-refinement crystallographic method (crystallographic refinement enhanced with quantum mechanical calculation) was adapted to treat the [AuL]/G-quadruplex structure, where each gold complex in the binding site was found spread over four equally occupied positions. The four positions were first determined by docking restrained to the crystallographically determined metal ions' coordinates. Then, the quantum refinement method was used to resolve the poorly defined density around the ligands and improve the crystallographic determination, revealing that the binding preferences of this metallodrug toward Tel24 G-quadruplex arise from a combined effect of pyrimidine stacking, metal–guanine interactions and charge–charge neutralizing action of the π-acid triazine. The occurrence of interaction in solution with the Tel24 G-quadruplex DNA was further proved through DNA melting experiments, which showed a slight destabilisation of the quadruplex upon adduct formation.
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| 9. |
- Jafari, Sonia, et al.
(författare)
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Benchmark Study of Redox Potential Calculations for Iron-Sulfur Clusters in Proteins
- 2022
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 61:16, s. 5991-6007
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Tidskriftsartikel (refereegranskat)abstract
- Redox potentials have been calculated for 12 different iron-sulfur sites of 6 different types with 1-4 iron ions. Structures were optimized with combined quantum mechanical and molecular mechanical (QM/MM) methods, and the redox potentials were calculated using the QM/MM energies, single-point QM methods in a continuum solvent or by QM/MM thermodynamic cycle perturbations. We show that the best results are obtained with a large QM system (∼300 atoms, but a smaller QM system, ∼150 atoms, can be used for the QM/MM geometry optimization) and a large value of the dielectric constant (80). For absolute redox potentials, the B3LYP density functional method gives better results than TPSS, and the results are improved with a larger basis set. However, for relative redox potentials, the opposite is true. The results are insensitive to the force field (charges of the surroundings) used for the QM/MM calculations or whether the protein and solvent outside the QM system are relaxed or kept fixed at the crystal structure. With the best approach for relative potentials, mean absolute and maximum deviations of 0.17 and 0.44 V, respectively, are obtained after removing a systematic error of -0.55 V. Such an approach can be used to identify the correct oxidation states involved in a certain redox reaction.
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| 10. |
- Justin, Bergmann, et al.
(författare)
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FragHAR : Towards ab initio quantum-crystallographic X-ray structure refinement for polypeptides and proteins
- 2020
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Ingår i: IUCrJ. - 2052-2525. ; 7:2, s. 158-165
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Tidskriftsartikel (refereegranskat)abstract
- The first ab initio aspherical structure refinement against experimental X-ray structure factors for polypeptides and proteins using a fragmentation approach to break up the protein into residues and solvent, thereby speeding up quantum-crystallographic Hirshfeld atom refinement (HAR) calculations, is described. It it found that the geometric and atomic displacement parameters from the new fragHAR method are essentially unchanged from a HAR on the complete unfragmented system when tested on dipeptides, tripeptides and hexapeptides. The largest changes are for the parameters describing H atoms involved in hydrogen-bond interactions, but it is shown that these discrepancies can be removed by including the interacting fragments as a single larger fragment in the fragmentation scheme. Significant speed-ups are observed for the larger systems. Using this approach, it is possible to perform a highly parallelized HAR in reasonable times for large systems. The method has been implemented in the TONTO software.
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| 11. |
- Singleton, Rosie K., et al.
(författare)
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Risk prediction for renal cell Carcinoma : Results from the European Prospective Investigation into Cancer and nutrition (EPIC) prospective cohort study
- 2021
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Ingår i: Cancer Epidemiology Biomarkers and Prevention. - : AACR. - 1055-9965 .- 1538-7755. ; 30:3, s. 507-512
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of renal cell carcinoma (RCC) has the potential to improve disease outcomes. No screening program for sporadic RCC is in place. Given relatively low incidence, screening would need to focus on people at high risk of clinically meaningful disease so as to limit overdiagnosis and screen-detected false positives. Methods: Among 192,172 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (including 588 incident RCC cases), we evaluated a published RCC risk prediction model (including age, sex, BMI, and smoking status) in terms of discrimination (C-statistic) and calibration (observed probability as a function of predicted probability). We used a flexible parametric survival model to develop an expanded model including age, sex, BMI, and smoking status, with the addition of self-reported history of hypertension and measured blood pressure. Results: The previously published model yielded well-calibrated probabilities and good discrimination (C-statistic [95% CI]: 0.699 [0.679–0.721]). Our model had slightly improved discrimination (0.714 [0.694–0.735], bootstrap optimism-corrected C-statistic: 0.709). Despite this good performance, predicted risk was low for the vast majority of participants, with 70% of participants having 10-year risk less than 0.0025. Conclusions: Although the models performed well for the prediction of incident RCC, they are currently insufficiently powerful to identify individuals at substantial risk of RCC in a general population. Impact: Despite the promising performance of the EPIC RCC risk prediction model, further development of the model, possibly including biomarkers of risk, is required to enable risk stratification of RCC.
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| 12. |
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The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
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Tidskriftsartikel (refereegranskat)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
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