| 1. |
- Billeter, Martin, 1955
(författare)
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A Consensus on Protein Structure Accuracy in NMR?
- 2015
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 23, s. 255-256
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The precision of anNMR structure may be manipulated by calculation parameters such as calibration factors. Its accuracy is, however, a different issue. In this issue of Structure, Buchner and Gu¨ ntert present ‘‘consensus structure bundles,’’ where precision analysis allows estimation of accuracy.
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| 2. |
- Billeter, Martin, 1955, et al.
(författare)
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Multi-way decomposition of projected spectra obtained in protein NMR
- 2007
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Ingår i: Proc. Appl. Math. Mech.. ; 7, s. 1110103-1110104
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Konferensbidrag (refereegranskat)abstract
- Multidimensional nuclear magnetic resonance spectroscopy is a highly versatile tool in protein research. Experimental limitations prohibit spectra with ≥ 5 dimensions. However, similar information can be obtained by recording 2-dimensional projections. A decomposition-based approach for analyzing projections is presented and applied to a protein. The resulting resonance identification is a prerequisite for further characterization of structure, dynamics and interactions of proteins.
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| 3. |
- Billeter, Martin, 1955
(författare)
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Non-uniform sampling in biomolecular NMR
- 2017
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Ingår i: Journal of Biomolecular Nmr. - : Springer Science and Business Media LLC. - 0925-2738 .- 1573-5001. ; 68:2, s. 65-66
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Billeter, Martin, 1955, et al.
(författare)
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Rapid Multidimensional NMR: Decomposition Methods and their Applications
- 2009
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Ingår i: Encyclopedia of Magnetic Resonance. - Chichester, UK : John Wiley & Sons, Ltd. ; 9
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Forskningsöversikt (refereegranskat)abstract
- A signal in an N-dimensional NMR spectrum can be characterized as a direct product of N Lorentzian functions, where each function characterizes the chemical shift and linewidth of the signal along one of the dimensions. Consequently, a complete spectrum (excluding noise) may be described in a compact form by a sum of direct products, one for each signal. This representation of a spectrum can in many cases be further compressed by characterizing several (related) signals with only one direct product. The description also applies to more general data sets, such as stacks of 2-dimensional spectra recorded for relaxation or drug discovery purposes, where the function type need no longer be Lorentzian. This view of NMR spectra serves as a basis for decomposition methods that provide a number of benefits for the interpretation of NMR data such as optimal processing with low signal-to-noise. A major interest in these decomposition tools has arisen in the context of ‘rapid’ NMR, for example with random sparse sampling of the time domain or with projection spectroscopy.
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| 5. |
- Billeter, Martin, 1955, et al.
(författare)
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Solution NMR structure determination of proteins revisited
- 2008
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Ingår i: J. Biomol. NMR. ; 42, s. 155-158
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Forskningsöversikt (refereegranskat)abstract
- This ‘Perspective’ bears on the present state of protein structure determination by NMR in solution. The focus is on a comparison of the infrastructure available for NMR structure determination when compared to protein crystal structure determination by X-ray diffraction. The main conclusion emerges that the unique potential of NMR to generate high resolution data also on dynamics, interactions and conformational equilibria has contributed to a lack of standard procedures for structure determination which would be readily amenable to improved efficiency by automation. To spark renewed discussion on the topic of NMR structure determination of proteins, procedural steps with high potential for improvement are identified.
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| 6. |
- Engman, Cecilia, 1974, et al.
(författare)
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DNA adopts normal B-form upon incorporation of highly fluorescent DNA base analogue tC: NMR structure and UV-Vis spectroscopy characterization
- 2004
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 32:17, s. 5087-95
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Tidskriftsartikel (refereegranskat)abstract
- The influence of the highly fluorescent tricyclic cytosine base analogue (tC) on duplex DNA conformation is investigated. The duplex properties are characterized by absorbance and circular dichroism (CD) for all combinations of neighbouring bases to tC, and an NMR structure is determined for one tC-containing sequence. For the oligonucleotides with one tC incorporated instead of cytosine, the melting temperature is increased on average by 2.7 degrees C above that for the unmodified ones. CD spectra are practically identical for modified and unmodified sequences, indicating an unperturbed B-DNA conformation. The NMR structure determination of the self-complementary sequence 5'-CTC(tC)ACGTGGAG shows a DNA conformation consistent with B-form for the whole duplex. The root-mean-square distance for the nucleotides of the eight central base pairs between the 10 structures with lowest CYANA target functions and a mean structure is 0.45 +/- 0.17 A. The NMR data confirm correct base pairing for tC by the observation of both intrastrand and interstrand imino proton NOEs. Altogether, this suggests that tC works well as a cytosine analogue, i.e. it is situated in the base stack, forming hydrogen bonds with G in the complementary strand, without distorting the DNA backbone conformation. This first example of an artificial, highly fluorescent DNA base that does not perturb the DNA conformation could have valuable applications for the study of the structure and dynamics of nucleic acid systems.
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| 7. |
- Eriksson, Emma S. E., et al.
(författare)
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De novo tertiary structure prediction using RNA123-benchmarking and application to Macugen
- 2014
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Ingår i: Journal of Molecular Modeling. - : Springer Science and Business Media LLC. - 1610-2940 .- 0948-5023. ; 20:8
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Tidskriftsartikel (refereegranskat)abstract
- The present benchmarking study utilizes the RNA123 program for de novo prediction of tertiary structures of a set of 50 RNA molecules for which X-ray/NMR structures are available, based on the nucleic acid sequence only. All molecules contain a hairpin loop motif and a helical structure of canonical and non-canonical base pairs, interrupted by bulges and internal loops to various degrees. RNA molecules with double helices made up purely by canonical base pairing, and molecules containing symmetric internal loops of non-canonical base pairing are, overall, very well predicted. Structures containing bulges and asymmetric internal loops, and more complex structures containing multiple bulges and internal loops in the same molecule, result in larger deviations from their X-ray/NMR predicted structures due to higher degree of flexibility of the nucleotide bases in these regions. In a majority of the molecules included herein, the RNA123 program was, however, able to predict the tertiary structure with a heavy atom RMSD of less than 5 angstrom to the X-ray/NMR structure, and the models were in most cases structurally closer to the X-ray/NMR structures than models predicted by MC-Fold and MC-Sym. A set of RNA molecules containing pseudoknot tertiary structure motifs were included, but neither of the programs was able to predict the folding of the single-stranded stem onto the helix without additional structural input. The RNA123 program was then applied to predict the tertiary structure of the RNA segment of Macugen (R), the first RNA aptamer approved for clinical use, and for which no tertiary structure has yet been solved. Four possible tertiary structures were predicted for this 27-nucleic-acid-long RNA molecule, which will be used in constructing a full model of the PEGylated aptamer and its interaction with the vascular endothelial growth factor target.
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| 8. |
- Fornander, Louise, 1984, et al.
(författare)
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Minor-Groove Binding Drugs: Where Is the Second Hoechst 33258 Molecule?
- 2013
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 117:19, s. 5820-5830
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Tidskriftsartikel (refereegranskat)abstract
- Hoechst 33258 binds with high affinity into the minor groove of AT-rich sequences of double-helical DNA. Despite extensive studies of this and analogous DNA binding molecules, there still remains uncertainty concerning the interactions when multiple ligand molecules are accommodated within close distance. Albeit not of direct concern for most biomedical applications, which are at low drug concentrations, interaction studies for higher drug binding are important as they can give fundamental insight into binding mechanisms and specificity, including drug self-stacking interactions that can provide base-sequence specificity. Using circular dichroism (CD), isothermal titration calorimetry (ITC), and proton nuclear magnetic resonance (1H NMR), we examine the binding of Hoechst 33258 to three oligonucleotide duplexes containing AT regions of different lengths: [d(CGCGAATTCGCG)]2 (A2T2), [d(CGCAAATTTGCG)]2 (A3T3), and [d(CGAAAATTTTCG)]2 (A4T4). We find similar binding geometries in the minor groove for all oligonucleotides when the ligand-to-duplex ratio is less than 1:1. At higher ratios, a second ligand can be accommodated in the minor groove of A4T4 but not A2T2 or A3T3. We conclude that the binding of the second Hoechst to A4T4 is not cooperative and that the molecules are sitting with a small separation apart, one after the other, and not in a sandwich structure as previously proposed.
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| 9. |
- Fredriksson, Jonas, 1972, et al.
(författare)
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Automated protein backbone assignment using the projection-decomposition approach
- 2012
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Ingår i: Journal of Biomolecular NMR. - 0925-2738. ; 54:1, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Spectral projection experiments by NMR in conjunction with decomposition analysis have been previously introduced for the backbone assignment of proteins; various pulse sequences as well as the behaviour with low signal-to-noise or chemical shift degeneracy have been illustrated. As a guide for routine applications of this combined tool, we provide here a systematic analysis on different types of proteins using welldefined run-time parameters. As a second result of this study, the backbone assignment module SHABBA was extensively rewritten and improved. Calculations on ubiquitin yielded again fully correct and nearly complete backbone and CHb assignments. For the 128 residue long azurin, missing assignments mostly affect Ha and Hb. Among the remaining backbone (plus Cb) nuclei 97.5 % could be assigned with 1.0 % differences to a reference. Finally, the new SHABBA algorithm was applied to projections recorded for a yeast histone protein domain at room temperature, where the protein is subject to partial unfolding: this leads to unobservable resonances (about a dozen missing signals in a normal 15N-HSQC) and extensive degeneracy among the resonances. From the clearly observable residues, 97.5 % of the backbone and CHbresonances could be assigned, of which only 0.8 % showed differences to published shifts. An additional study on the protein MMP20, which exhibits spectral difficulties to an even larger extent, explores the limitations of the approach.
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| 10. |
- Fredriksson, Jonas, 1972, et al.
(författare)
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Complete protein assignment from sets of spectra recorded overnight
- 2019
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Ingår i: Journal of Biomolecular NMR. - : Springer Science and Business Media LLC. - 0925-2738 .- 1573-5001. ; 73:1-2, s. 59-70
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Tidskriftsartikel (refereegranskat)abstract
- A flexible and scalable approach for protein NMR is introduced that builds on rapid data collection via projection spectroscopy and analysis of the spectral input data via joint decomposition. Input data may originate from various types of spectra, depending on the ultimate goal: these may result from experiments based on triple-resonance pulse sequences, or on TOCSY or NOESY sequences, or mixtures thereof. Flexible refers to the free choice of spectra for the joint decompositions depending on the purpose: assignments, structure, dynamics, interactions. Scalable means that the approach is open to the addition of similar or different experiments, e.g. larger proteins may require a wider selection of triple-resonance based experiments. Central to the proposed approach is the mutual support among the different spectra during the spectral analysis: for example, sparser triple-resonance spectra may help decomposing (separating) spin systems in a TOCSY or identifying unique NOEs. In the example presented, backbone plus side chain assignments of ubiquitin were obtained from the combination of either two or three of the following projection experiments: a 4D HCCCONH, a 4D HNCACO and a 3D HNCACB. In all cases, TOCSY data (4D HCCCONH) proved crucial not only for the side chain assignments, but also for the sequential assignment. Even when total recording time was reduced to about 10 h, nearly complete assignments were obtained, with very few missing assignments and even fewer differences to a reference.
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