TY  - JOUR
AB  - The presence of an unpaired electron in paramagnetic molecules generates significant effects in NMR spectra, which can be exploited to provide restraints complementary to those used in standard structure-calculation protocols. NMR already occupies a central position in drug discovery for its use in fragment screening, structural biology and validation of ligand-target interactions. Paramagnetic restraints provide unique opportunities, for example, for more sensitive screening to identify weaker-binding fragments. A key application of paramagnetic NMR in drug discovery, however, is to provide new structural restraints in cases where crystallography proves intractable. This is particularly important at early stages in drug-discovery programs where crystal structures of weakly-binding fragments are difficult to obtain and crystallization artefacts are probable, but structural information about ligand poses is crucial to guide medicinal chemistry. Numerous applications show the value of paramagnetic restraints to filter computational docking poses and to generate interaction models. Paramagnetic relaxation enhancements (PREs) generate a distance-dependent effect, while pseudo-contact shift (PCS) restraints provide both distance and angular information. Here, we review strategies for introducing paramagnetic centers and discuss examples that illustrate the utility of paramagnetic restraints in drug discovery. Combined with standard approaches, such as chemical shift perturbation and NOE-derived distance information, paramagnetic NMR promises a valuable source of information for many challenging drug-discovery programs.
AU  - Softley, C.
AU  - Bostock, M.J.
AU  - Popowicz, G.M.
AU  - Sattler, M.
C1  - 59349
C2  - 48753
CY  - Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands
SP  - 287–309
TI  - Paramagnetic NMR in drug discovery.
JO  - J. Biomol. NMR
VL  - 74
PB  - Springer
PY  - 2020
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - The physiological role of proteins is frequently linked to interactions with non-protein ligands or posttranslational modifications. Structural characterization of these complexes or modified proteins by NMR may be difficult as the ligands are usually not available in an isotope-labeled form and NMR spectra may suffer from signal overlap. Here, we present an optimized approach that uses specific NMR isotope-labeling schemes for overcoming both hurdles. This approach enabled the high-resolution structure determination of the farnesylated C-terminal domain of the peroxisomal protein PEX19. The approach combines specific C-13, N-15 and H-2 isotope labeling with tailored NMR experiments to (i) unambiguously identify the NMR frequencies and the stereochemistry of the unlabeled 15-carbon isoprenoid, (ii) resolve the NMR signals of protein methyl groups that contact the farnesyl moiety and (iii) enable the unambiguous assignment of a large number of protein-farnesyl NOEs. Protein deuteration was combined with selective isotope-labeling and protonation of amino acids and methyl groups to resolve ambiguities for key residues that contact the farnesyl group. Sidechain-labeling of leucines, isoleucines, methionines, and phenylalanines, reduced spectral overlap, facilitated assignments and yielded high quality NOE correlations to the unlabeled farnesyl. This approach was crucial to enable the first NMR structure of a farnesylated protein. The approach is readily applicable for NMR structural analysis of a wide range of protein-ligand complexes, where isotope-labeling of ligands is not well feasible.
AU  - Tripsianes, K.*
AU  - Schütz, U.
AU  - Emmanouilidis, L.
AU  - Gemmecker, G.
AU  - Sattler, M.
C1  - 55964
C2  - 46724
CY  - Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands
SP  - 183-189
TI  - Selective isotope labeling for NMR structure determination of proteins in complex with unlabeled ligands.
JO  - J. Biomol. NMR
VL  - 73
IS  - 3-4
PB  - Springer
PY  - 2019
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - Quantification of dipolar couplings in biological solids is important for the understanding of dynamic processes. Under Magic Angle Spinning (MAS), order parameters are normally obtained by recoupling of anisotropic interactions involving the application of radio frequency pulses. We have recently shown that amide backbone order parameters can be estimated accurately in a spin-echo experiment in case the rotor spinning angle is slightly mis-calibrated. In this work, we apply this method to determine methyl order parameters in a deuterated sample of the SH3 domain of chicken a-spectrin in which the methyl containing side chains valine and leucine are selectively protonated.
AU  - Xue, K.
AU  - Mamone, S.*
AU  - Koch, B.
AU  - Sarkar, R.
AU  - Reif, B.
C1  - 56745
C2  - 47255
CY  - Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands
SP  - 471-475
TI  - Determination of methyl order parameters using solid state NMR under off magic angle spinning.
JO  - J. Biomol. NMR
VL  - 73
IS  - 8-9
PB  - Springer
PY  - 2019
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - Sensitivity and resolution together determine the quality of NMR spectra in biological solids. For high-resolution structure determination with solid-state NMR, proton-detection emerged as an attractive strategy in the last few years. Recent progress in probe technology has extended the range of available MAS frequencies up to above 100 kHz, enabling the detection of resolved resonances from sidechain protons, which are important reporters of structure. Here we characterise the interplay between MAS frequency in the newly available range of 70-110 kHz and proton content on the spectral quality obtainable on a 1 GHz spectrometer for methyl resonances. Variable degrees of proton densities are tested on microcrystalline samples of the alpha-spectrin SH3 domain with selectively protonated methyl isotopomers (CH3, CH2D, CHD2) in a perdeuterated matrix. The experimental results are supported by simulations that allow the prediction of the sensitivity outside this experimental frequency window. Our results facilitate the selection of the appropriate labelling scheme at a given MAS rotation frequency.
AU  - Xue, K.
AU  - Sarkar, R.
AU  - Tosner, Z.*
AU  - Lalli, D.*
AU  - Motz, C.*
AU  - Koch, B.*
AU  - Pintacuda, G.*
AU  - Reif, B.
C1  - 56899
C2  - 47364
CY  - Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands
SP  - 625-631
TI  - MAS dependent sensitivity of different isotopomers in selectively methyl protonated protein samples in solid state NMR.
JO  - J. Biomol. NMR
VL  - 73
IS  - 10-11
PB  - Springer
PY  - 2019
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - In this work, we show how the water flip-back approach that is widely employed in solution-state NMR can be adapted to proton-detected MAS solid-state NMR of highly deuterated proteins. The scheme allows to enhance the sensitivity of the experiment by decreasing the recovery time of the proton longitudinal magnetization. The method relies on polarization transfer from non-saturated water to the protein during the inter-scan delay.
AU  - Chevelkov, V.*
AU  - Xiang, S.*
AU  - Giller, K.*
AU  - Becker, S.T.*
AU  - Lange, A.D.*
AU  - Reif, B.
C1  - 43223
C2  - 36327
CY  - Dordrecht
SP  - 151-160
TI  - Perspectives for sensitivity enhancement in proton-detected solid-state NMR of highly deuterated proteins by preserving water magnetization.
JO  - J. Biomol. NMR
VL  - 61
IS  - 2
PB  - Springer
PY  - 2015
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - NMR studies of multi-domain protein complexes provide unique insight into their molecular interactions and dynamics in solution. For large proteins domain-selective isotope labeling is desired to reduce signal overlap, but available methods require extensive optimization and often give poor ligation yields. We present an optimized strategy for segmental labeling of multi-domain proteins using the S. aureus transpeptidase Sortase A. Critical improvements compared to existing protocols are (1) the efficient removal of cleaved peptide fragments by centrifugal filtration and (2) a strategic design of cleavable and non-cleavable affinity tags for purification. Our approach enables routine production of milligram amounts of purified segmentally labeled protein for NMR and other biophysical studies.
AU  - Freiburger, L.
AU  - Sonntag, M.
AU  - Hennig, J.
AU  - Li, J.*
AU  - Zou, P.
AU  - Sattler, M.
C1  - 46689
C2  - 37715
SP  - 1-8
TI  - Efficient segmental isotope labeling of multi-domain proteins using Sortase A.
JO  - J. Biomol. NMR
VL  - 63
IS  - 1
PY  - 2015
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - We have developed an approach for simultaneous structure calculation and automatic Nuclear Overhauser Effect (NOE) assignment to solve nuclear magnetic resonance (NMR) structures from unassigned NOESY data. The approach, autoNOE-Rosetta, integrates Resolution Adapted Structural RECombination (RASREC) Rosetta NMR calculations with algorithms for automatic NOE assignment. The method was applied to two proteins in the 15-20 kDa size range for which both, NMR and X-ray data, is available. The autoNOE-Rosetta calculations converge for both proteins and yield accurate structures with an RMSD of 1.9 Å to the X-ray reference structures. The method greatly expands the radius of convergence for automatic NOE assignment, and should be broadly useful for NMR structure determination.
AU  - Lange, O.F.
C1  - 31534
C2  - 34532
CY  - Dordrecht
SP  - 147-159
TI  - Automatic NOESY assignment in CS-RASREC-Rosetta.
JO  - J. Biomol. NMR
VL  - 59
IS  - 3
PB  - Springer
PY  - 2014
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - Aggregates formed by amyloidogenic peptides and proteins and reconstituted membrane protein preparations differ significantly in terms of the spectral quality that they display in solid-state NMR experiments. Structural heterogeneity and dynamics can both in principle account for that observation. This perspectives article aims to point out challenges and limitations, but also potential opportunities in the investigation of these systems.
AU  - Linser, R.*
AU  - Sarkar, R.
AU  - Krushelnitzky, A.*
AU  - Mainz, A.
AU  - Reif, B.
C1  - 30747
C2  - 33866
CY  - Dordrecht
SP  - 1-14
TI  - Dynamics in the solid-state: Perspectives for the investigation of amyloid aggregates, membrane proteins and soluble protein complexes.
JO  - J. Biomol. NMR
VL  - 59
IS  - 1
PB  - Springer
PY  - 2014
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - Relaxation parameters such as longitudinal relaxation are susceptible to artifacts such as spin diffusion, and can be affected by paramagnetic impurities as e.g. oxygen, which make a quantitative interpretation difficult. We present here the site-specific measurement of [1H]13C and [1H]15N heteronuclear rates in an immobilized protein. For methyls, a strong effect is expected due to the three-fold rotation of the methyl group. Quantification of the [1H]13C heteronuclear NOE in combination with 13C-R1 can yield a more accurate analysis of side chain motional parameters. The observation of significant [1H]15N heteronuclear NOEs for certain backbone amides, as well as for specific asparagine/glutamine sidechain amides is consistent with MD simulations. The measurement of site-specific heteronuclear NOEs is enabled by the use of highly deuterated microcrystalline protein samples in which spin diffusion is reduced in comparison to protonated samples.
AU  - Lopez del Amo, J.M.
AU  - Agarwal, V.*
AU  - Sarkar, R.
AU  - Porter, J.
AU  - Asami, S.
AU  - Rübbelke, M.
AU  - Fink, U.*
AU  - Xue, Y.*
AU  - Lange, O.F.
AU  - Reif, B.
C1  - 31756
C2  - 36320
CY  - Dordrecht
SP  - 241-249
TI  - Site-specific analysis of heteronuclear Overhauser effects in microcrystalline proteins.
JO  - J. Biomol. NMR
VL  - 59
IS  - 4
PB  - Springer
PY  - 2014
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - We have developed a novel and robust approach for automatic and unsupervised simultaneous nuclear Overhauser effect (NOE) assignment and structure determination within the CS-Rosetta framework. Starting from unassigned peak lists and chemical shift assignments, autoNOE-Rosetta determines NOE cross-peak assignments and generates structural models. The approach tolerates incomplete and raw NOE peak lists as well as incomplete or partially incorrect chemical shift assignments, and its performance has been tested on 50 protein targets ranging from 50 to 200 residues in size. We find a significantly improved performance compared to established programs, particularly for larger proteins and for NOE data obtained on perdeuterated protein samples. X-ray crystallographic structures allowed comparison of Rosetta and conventional, PDB-deposited, NMR models in 20 of 50 test cases. The unsupervised autoNOE-Rosetta models were often of significantly higher accuracy than the corresponding expert-supervised NMR models deposited in the PDB. We also tested the method with unrefined peak lists and found that performance was nearly as good as for refined peak lists. Finally, demonstrating our method's remarkable robustness against problematic input data, we provided correct models for an incorrect PDB-deposited NMR solution structure.
AU  - Zhang, Z.*
AU  - Porter, J.*
AU  - Tripsianes, K.*
AU  - Lange, O.F.
C1  - 31575
C2  - 34560
CY  - Dordrecht
SP  - 135-145
TI  - Robust and highly accurate automatic NOESY assignment and structure determination with Rosetta.
JO  - J. Biomol. NMR
VL  - 59
IS  - 3
PB  - Springer
PY  - 2014
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - Many processes in the regulation of gene expression and signaling involve the formation of protein complexes involving multi-domain proteins. Individual domains that mediate protein-protein and protein-nucleic acid interactions are typically connected by flexible linkers, which contribute to conformational dynamics and enable the formation of complexes with distinct binding partners. Solution techniques are therefore required for structural analysis and to characterize potential conformational dynamics. Nuclear magnetic resonance spectroscopy (NMR) provides such information but often only sparse data are obtained with increasing molecular weight of the complexes. It is therefore beneficial to combine NMR data with additional structural restraints from complementary solution techniques. Small angle X-ray/neutron scattering (SAXS/SANS) data can be efficiently combined with NMR-derived information, either for validation or by providing additional restraints for structural analysis. Here, we show that the combination of SAXS and SANS data can help to refine structural models obtained from data-driven docking using HADDOCK based on sparse NMR data. The approach is demonstrated with the ternary protein-protein-RNA complex involving two RNA recognition motif (RRM) domains of Sex-lethal, the N-terminal cold shock domain of Upstream-to-N-Ras, and msl-2 mRNA. Based on chemical shift perturbations we have mapped protein-protein and protein-RNA interfaces and complemented this NMR-derived information with SAXS data, as well as SANS measurements on subunit-selectively deuterated samples of the ternary complex. Our results show that, while the use of SAXS data is beneficial, the additional combination with contrast variation in SANS data resolves remaining ambiguities and improves the docking based on chemical shift perturbations of the ternary protein-RNA complex.
AU  - Hennig, J.
AU  - Wang, I.
AU  - Sonntag, M.
AU  - Gabel, F.*
AU  - Sattler, M.
C1  - 26154
C2  - 32096
SP  - 17-30
TI  - Combining NMR and small angle X-ray and neutron scattering in the structural analysis of a ternary protein-RNA complex.
JO  - J. Biomol. NMR
VL  - 56
IS  - 1
PB  - Springer
PY  - 2013
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - Dynamic Nuclear Polarization solid-state NMR holds the potential to enable a dramatic increase in sensitivity by exploiting the large magnetic moment of the electron. However, applications to biological solids are hampered in uniformly isotopically enriched biomacromolecules due to line broadening which yields a limited spectral resolution at cryogenic temperatures. We show here that high magnetic fields allow to overcome the broadening of resonance lines often experienced at liquid nitrogen temperatures. For a fibril sample of the Alzheimer's disease β-amyloid peptide, we find similar line widths at low temperature and at room temperature. The presented results open new perspectives for structural investigations in the solid-state.
AU  - Lopez del Amo, J.M.
AU  - Schneider, D.*
AU  - Loquet, A.*
AU  - Lange, A.*
AU  - Reif, B.
C1  - 26176
C2  - 32107
SP  - 359-363
TI  - Cryogenic solid state NMR studies of fibrils of the Alzheimer's disease amyloid-β peptide: Perspectives for DNP.
JO  - J. Biomol. NMR
VL  - 56
IS  - 4
PB  - Springer
PY  - 2013
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - We report advances in the calculation of protein structures from chemical shift nuclear magnetic resonance data alone. Our previously developed method, CS-Rosetta, assembles structures from a library of short protein fragments picked from a large library of protein structures using chemical shifts and sequence information. Here we demonstrate that combination of a new and improved fragment picker and the iterative sampling algorithm RASREC yield significant improvements in convergence and accuracy. Moreover, we introduce improved criteria for assessing the accuracy of the models produced by the method. The method was tested on 39 proteins in the 50-100 residue size range and yields reliable structures in 70 % of the cases. All structures that passed the reliability filter were accurate (<2 Å RMSD from the reference).
AU  - van der Schot, G.*
AU  - Zhang, Z.*
AU  - Vernon, R.*
AU  - Shen, Y.*
AU  - Vranken, W.F.*
AU  - Baker, D.*
AU  - Bonvin, A.M.*
AU  - Lange, O.F.
C1  - 26539
C2  - 32290
SP  - 27-35
TI  - Improving 3D structure prediction from chemical shift data.
JO  - J. Biomol. NMR
VL  - 57
IS  - 1
PB  - Springer
PY  - 2013
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - A new fragment picker has been developed for CS-Rosetta that combines beneficial features of the original fragment picker, MFR, used with CS-Rosetta, and the fragment picker, NNMake, that was used for purely sequence based fragment selection in the context of ROSETTA de-novo structure prediction. Additionally, the new fragment picker has reduced sensitivity to outliers and other difficult to match data points rendering the protocol more robust and less likely to introduce bias towards wrong conformations in cases where data is bad, missing or inconclusive. The fragment picker protocol gives significant improvements on 6 of 23 CS-Rosetta targets. An independent benchmark on 39 protein targets, whose NMR data sets were published only after protocol optimization had been finished, also show significantly improved performance for the new fragment picker.
AU  - Vernon, R.*
AU  - Shen, Y.*
AU  - Baker, D.*
AU  - Lange, O.F.
C1  - 27451
C2  - 32676
SP  - 117-127
TI  - Improved chemical shift based fragment selection for CS-Rosetta using Rosetta3 fragment picker.
JO  - J. Biomol. NMR
VL  - 57
IS  - 2
PB  - Springer
PY  - 2013
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - Biological solid-state nuclear magnetic resonance spectroscopy developed rapidly in the past two decades and emerged as an important tool for structural biology. Resonance assignment is an essential prerequisite for structure determination and the characterization of motional properties of a molecule. Experiments, which rely on carbon or nitrogen detection, suffer, however, from low sensitivity. Recently, we introduced the RAP (Reduced Adjoining Protonation) labeling scheme, which allows to detect backbone and sidechain protons with high sensitivity and resolution. We present here a (1)H-detected 3D (H)CCH experiment for assignment of backbone and sidechain proton resonances. Resolution is significantly improved by employing simultaneous (13)CO and (13)Cβ J-decoupling during evolution of the (13)Cα chemical shift. In total, ~90% of the (1)Hα-(13)Cα backbone resonances of chicken α-spectrin SH3 could be assigned.
AU  - Asami, S.*
AU  - Reif, B.
C1  - 7222
C2  - 29567
SP  - 31-39
TI  - Assignment strategies for aliphatic protons in the solid-state in randomly protonated proteins.
JO  - J. Biomol. NMR
VL  - 52
IS  - 1
PB  - Springer
PY  - 2012
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - The H-1 dipolar network, which is the major obstacle for applying proton detection in the solid-state, can be reduced by deuteration, employing the RAP (Reduced Adjoining Protonation) labeling scheme, which yields random protonation at non-exchangeable sites. We present here a systematic study on the optimal degree of random sidechain protonation in RAP samples as a function of the MAS (magic angle spinning) frequency. In particular, we compare H-1 sensitivity and linewidth of a microcrystalline protein, the SH3 domain of chicken alpha-spectrin, for samples, prepared with 5-25 % H2O in the E. coli growth medium, in the MAS frequency range of 20-60 kHz. At an external field of 19.96 T (850 MHz), we find that using a proton concentration between 15 and 25 % in the M9 medium yields the best compromise in terms of sensitivity and resolution, with an achievable average H-1 linewidth on the order of 40-50 Hz. Comparing sensitivities at a MAS frequency of 60 versus 20 kHz, a gain in sensitivity by a factor of 4-4.5 is observed in INEPT-based H-1 detected 1D H-1,C-13 correlation experiments. In total, we find that spectra recorded with a 1.3 mm rotor at 60 kHz have almost the same sensitivity as spectra recorded with a fully packed 3.2 mm rotor at 20 kHz, even though similar to 20x less material is employed. The improved sensitivity is attributed to H-1 line narrowing due to fast MAS and to the increased efficiency of the 1.3 mm coil.
AU  - Asami, S.
AU  - Szekely, K.*
AU  - Schanda, P.*
AU  - Meier, B.H.*
AU  - Reif, B.
C1  - 10620
C2  - 30349
SP  - 155-168
TI  - Optimal degree of protonation for 1H detection of aliphatic sites in randomly deuterated proteins as a function of the MAS frequency.
JO  - J. Biomol. NMR
VL  - 54
IS  - 2
PB  - Springer
PY  - 2012
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - We present the quantification of backbone amide hydrogen-deuterium exchange rates (HDX) for immobilized proteins. The experiments make use of the deuterium isotope effect on the amide nitrogen chemical shift, as well as on proton dilution by deuteration. We find that backbone amides in the microcrystalline α-spectrin SH3 domain exchange rather slowly with the solvent (with exchange rates negligible within the individual (15)N-T (1) timescales). We observed chemical exchange for 6 residues with HDX exchange rates in the range from 0.2 to 5 s(-1). Backbone amide (15)N longitudinal relaxation times that we determined previously are not significantly affected for most residues, yielding no systematic artifacts upon quantification of backbone dynamics (Chevelkov et al. 2008b). Significant exchange was observed for the backbone amides of R21, S36 and K60, as well as for the sidechain amides of N38, N35 and for W41ε. These residues could not be fit in our previous motional analysis, demonstrating that amide proton chemical exchange needs to be considered in the analysis of protein dynamics in the solid-state, in case D(2)O is employed as a solvent for sample preparation. Due to the intrinsically long (15)N relaxation times in the solid-state, the approach proposed here can expand the range of accessible HDX rates in the intermediate regime that is not accessible so far with exchange quench and MEXICO type experiments.
AU  - Lopez del Amo, J.M.*
AU  - Fink, U.*
AU  - Reif, B.
C1  - 3109
C2  - 28035
SP  - 203-212
TI  - Quantification of protein backbone hydrogen-deuterium exchange rates by solid state NMR spectroscopy.
JO  - J. Biomol. NMR
VL  - 48
IS  - 4
PB  - Springer
PY  - 2010
SN  - 0925-2738
ER  - 

TY  - JOUR
AB  - We present the implementation of a target function based on Small Angle Scattering data (Gabel et al.Eur Biophys J 35(4):313-327, 2006) into the Crystallography and NMR Systems (CNS) and demonstrate its utility in NMR structure calculations by simultaneous application of small angle scattering (SAS) and residual dipolar coupling (RDC) restraints. The efficiency and stability of the approach are demonstrated by reconstructing the structure of a two domain region of the 31 kDa nuclear export factor TAP(TIP-associated protein). Starting with the high resolution X-ray structures of the two individual TAP domains, the translational and orientational domain arrangement is refined simultaneously. We tested the stability of the protocol against variations of the SAS target parameters and the number of RDCs and their uncertainties. The activation of SAS restraints results in an improved translational clustering of the domain positions and lifts part of the fourfold degeneracy of their orientations (associated with a single alignment tensor). The resulting ensemble of structures reflects the conformational space that is consistent with the experimental SAS and RDC data. The SAS target function is computationally very efficient. SAS restraints can be activated at different levels or precision and only a limited SAS angular range is required. When combined with additional data from chemical shift perturbation, paramagnetic relaxation enhancement or mutational analysis the SAS refinement is an efficient approach for defining the topology of multi-domain and/or multimeric biomolecular complexes in solution based on available high resolution structures (NMR or X-ray) of the individual domains.
AU  - Gabel, F.*
AU  - Simon, B.*
AU  - Nilges, M.*
AU  - Petoukhov, M.*
AU  - Svergun, D.*
AU  - Sattler, M.
C1  - 4517
C2  - 25939
SP  - 199-208
TI  - A structure refinement protocol combining NMR residual dipolar couplings and small angle scattering restraints.
JO  - J. Biomol. NMR
VL  - 41
IS  - 4
PB  - Springer
PY  - 2008
SN  - 0925-2738
ER  -