Biomedical subjects

Daniel Malmodin

Publications and source records attributed to Daniel Malmodin.

4 recordsLinked to original sources

PubMed2006

Robust and versatile interpretation of spectra with coupled evolution periods using multi-way decomposition.

Coupling of evolution periods in NMR experiments is a very promising approach that has recently attracted much attention for its substantial savings in measurement time. Another novel concept, which has already proved useful in many types of NMR applications is multi-way decomposition. The PRODECOMP tool described here addresses the combination of these two modern tools in protein NMR. The following properties of this approach are described and illustrated. Highly similar information to what would be found in a corresponding full-dimensional spectrum is extracted from a set of projected spectra. All experimental spectra are used simultaneously, avoiding sensitivity loss associated with individual examination of the spectra. Aliasing caused by the linear combinations of individual shifts in the projected spectra is automatically resolved, allowing for better resolution due to smaller spectral widths. Reconstructions of various high-dimensional spectra, including the corresponding full-dimensional spectrum become straightforward. Spectral overlap is efficiently resolved. The capabilities of PRODECOMP are illustrated for a 14 kD protein, for which 12 projections of a 5-dimensional spectrum with the nuclei N, HN, CO, Calpha and Halpha are analysed.

Algorithms↗

PubMed2005

Multiway decomposition of NMR spectra with coupled evolution periods.

Coupling evolution periods in NMR experiments on proteins has recently attracted much attention for its substantial savings in measurement time. Using the concept of multiway decomposition, which already proved useful in many types of NMR applications, the novel tool PRODECOMP decomposes sets of spectra with coupled evolution periods and attempts to provide all information that would be found in a corresponding full-dimensional spectrum. It offers the following advantages: (1) all experimental spectra are used simultaneously, avoiding sensitivity loss associated with individual examination of the spectra, (2) folding (aliasing) caused by the linear combinations of individual shifts in the projected spectra is automatically resolved, allowing for better resolution due to smaller spectral widths, (3) various types of schemes for the coupling of evolution periods are possible, (4) reconstructions of various high-dimensional spectra, including the corresponding full-dimensional spectrum, are straightforward, (5) overlap in both the projected and the directly detected dimensions is efficiently resolved. The capabilities of PRODECOMP are illustrated for a 14 kD protein, for which 12 projections of a five-dimensional spectrum with the nuclei N, HN, CO, Calpha, and Halpha are analyzed.

Journal Article↗

PubMed2005

Signal identification in NMR spectra with coupled evolution periods.

Novel multidimensional NMR experiments rely on modified time-domain sampling schemes to provide significant savings of experimental time. Several approaches are based on the coupling of evolution times resulting in a reduction of the dimensionality of the recorded spectra, and a concomitant saving of experimental time. We present a consistent and general tool, called EVOCOUP, for the analysis of these reduced dimensionality spectra. The approach is flexible in the sense that the input can consist of various forms of reduced dimensionality spectra, that any piece of information can be removed (provided enough information is left), e.g., signals undetectable due to poor signal-to-noise or covered by artifacts, and that it can be applied to spectra involving any number of nuclei. The use of a general optimization procedure and an appropriate target function provides for a robust approach with well-defined results and ensures optimal use of redundant information normally present in the input. Spectral overlap in the directly detected dimension is resolved in a fully automated manner, avoiding the assessment of signal quality and its use in combinatorial trials. The positions of all peaks in a corresponding full-dimensional spectrum are obtained without need for reconstruction of this spectrum. In a systematic analysis of a complete spectrum recorded for the 14 kDa protein azurin and involving five different nuclei, only four spin systems were missed and no false spins systems were detected.

Artifacts↗

PubMed2003

Fully automated sequence-specific resonance assignments of hetero- nuclear protein spectra.

Full automation of the analysis of spectra is a prerequisite for high-throughput NMR studies in structural or functional genomics. Sequence-specific assignments often form the major bottleneck. Here, we present a procedure that yields nearly complete backbone and side chain resonance assignments starting from a set of heteronuclear three-dimensional spectra. Neither manual intervention, e.g., to correct lists obtained from peak picking before feeding these to an assignment program, nor protein-specific information, e.g., structures of homologous proteins, were required. By combining two earlier published procedures, AUTOPSY [Koradi et al. (1998) J. Magn. Reson., 135, 288-297] and GARANT [Bartels et al. (1996) J. Biomol. NMR, 7, 207-213], with a new program, PICS, all necessary steps from spectra analyses to sequence-specific assignments were performed fully automatically. Characteristic features of the present approach are a flexible design allowing as input almost any combination of NMR spectra, applicability to side chains, robustness with respect to parameter choices (such as noise levels) and reproducibility. In this study, automated resonance assignments were obtained for the 14 kD blue copper protein azurin from P. aeruginosa using five spectra: HNCACB, HNHA, HCCH-TOCSY, 15N-NOESY-HSQC and 13C-NOESY-HSQC. Peaks from these three-dimensional spectra were filtered and calibrated with the help of two two-dimensional spectra: 15N-HSQC and 13C-HSQC. The rate of incorrect assignments is less than 1.5% for backbone nuclei and about 3.5% when side chain protons are also considered.

Azurin↗