CORCEMA evaluation of the potential role of intermolecular transferred NOESY in the characterization of ligand-receptor complexes

Curto, Ernest V.; Moseley, Hunter N. B.; Krishna, N. Rama

doi:10.1007/bf00124470

Cited by 19 publications

(21 citation statements)

References 46 publications

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“…Additionally, the ligand poses of our NMR-guided PLANTS docking might serve as ideal starting points for a more sophisticated refinement. The CORCEMA [41,42] and CORCE-MA-ST [43,44] approach based on the full calculation of the relaxation and conformational exchange matrix could be used for trNOE and STD data, respectively. However, owing to the large amount of computer time needed for these calculations, these would be applied in a post-processing step for rescoring the generated poses.…”

Section: Discussionmentioning

confidence: 99%

NMR‐Guided Molecular Docking of a Protein–Peptide Complex Based on Ant Colony Optimization

Korb¹,

Möller²,

Exner³

2010

ChemMedChem

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Standard docking approaches used for the prediction of protein-ligand complexes in the drug development process have problems identifying the correct binding mode of large flexible ligands. Herein we show how additional experimental data from NMR experiments can be used to predict the binding mode of a mucin 1 (MUC-1) pentapeptide recognized by the breast-cancer-selective monoclonal antibody SM3. Distance constraints derived from trNOE and saturation transfer difference NMR experiments are combined with the docking approach PLANTS. The resulting complex structures show excellent agreement with the NMR data and with a published X-ray crystal structure. The method was then further tested on two complexes in order to demonstrate its more general applicability: T-antigen disaccharide bound to Maclura pomifera agglutinin, and the inhibitor SBi279 bound to S100B protein. Our new approach has the advantages of being fully automatic, rapid, and unbiased; moreover, it is based on relatively easily obtainable experimental data and can greatly increase the reliability of the generated structures.

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Section: Discussionmentioning

confidence: 99%

NMR‐Guided Molecular Docking of a Protein–Peptide Complex Based on Ant Colony Optimization

Korb¹,

Möller²,

Exner³

2010

ChemMedChem

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“…Example methods include SOS-NMR [45,47], NOE matching [49], INPHARMA [48,66,67], CORCEMA [46,68,69], or NMR 2 [32,33]. Except for NMR 2 , these methods require a docking step prior to the experimentally based scoring of the found poses and eventually perform an experimentally based refinement step.…”

Section: Nmr 2 Versus Other Methods For Rapid Structure Calculations mentioning

confidence: 99%

“…CORCEMA [46,68,69] and INPHARMA [48,67,72,73] are methods that back predict intra-ligand, intra-protein and protein-ligand NOEs or spin diffusion using the full relaxation matrix formalism. They are powerful tools that can also handle systems undergoing multistate conformational exchange and chemical exchange between the free and bound states.…”

Section: Nmr 2 Versus Other Methods For Rapid Structure Calculations mentioning

confidence: 99%

The NMR2 Method to Determine Rapidly the Structure of the Binding Pocket of a Protein–Ligand Complex with High Accuracy

Wälti

Orts

2018

Magnetochemistry

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Structural characterization of complexes is crucial for a better understanding of biological processes and structure-based drug design. However, many protein-ligand structures are not solvable by X-ray crystallography, for example those with low affinity binders or dynamic binding sites. Such complexes are usually targeted by solution-state NMR spectroscopy. Unfortunately, structure calculation by NMR is very time consuming since all atoms in the complex need to be assigned to their respective chemical shifts. To circumvent this problem, we recently developed the Nuclear Magnetic Resonance Molecular Replacement (NMR 2 ) method. NMR 2 very quickly provides the complex structure of a binding pocket as measured by solution-state NMR. NMR 2 circumvents the assignment of the protein by using previously determined structures and therefore speeds up the whole process from a couple of months to a couple of days. Here, we recall the main aspects of the method, show how to apply it, discuss its advantages over other methods and outline its limitations and future directions.

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“…A simple analysis of the NOESY spectra (Gronenborn and Clore, 1982) yielded conflicting distance estimates. This implies that a more detailed dynamical model must be applied (Curto et al, 1996).…”

Section: Downloaded Frommentioning

confidence: 99%

Opioids Bind to the Amino Acids 84 to 118 of UDP-Glucuronosyltransferase UGT2B7

Coffman

Kearney²,

Goldsmith³

et al. 2003

Mol Pharmacol

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The UDP-glucuronosyltransferase UGT2B7 is an important human UGT isoform that catalyzes the conjugation of many endogenous and exogenous compounds, among them opioids, resulting in the formation of D-glucuronides. The binding site of the aglycone is located in the N-terminal half of the protein.Using NMR analysis, we demonstrate that the opioid binding site in UGT2B7 is within the 84 to 118 N-terminal amino acids. Three maltose binding protein-UGT2B7 fusion proteins, 2B7F3 and 2B7F4 incorporating the amino acids 24 to 118 and 24 to 96 of UGT2B7, respectively, and 2B7F5 incorporating amino acids 84 to 118 of UGT2B7 were expressed in Escherichia coli and purified by affinity chromatography. NMR analysis showed that morphine was bound to the fusion protein 2B7F3 with a K D value similar to the K D values obtained for the previously produced fusion proteins, which included amino acids 24 to 180. Morphine did not bind to 2B7F4, but it did bind to 2B7F5. Both NMR 1-D spectra and NOESY experiments indicated that the 2B7F5 protein was mediating magnetization transfer within the morphine. These results allowed us to predict and model a binding site within the amino acids 96 to 101 of UGT2B7. A mutant fusion protein 2B7F3 with the substitution D99A was produced, and the NMR spectroscopy analysis of the protein supported the model. A marked reduction of morphine binding was observed when the charged aspartate was substituted with alanine.

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CORCEMA evaluation of the potential role of intermolecular transferred NOESY in the characterization of ligand-receptor complexes

Cited by 19 publications

References 46 publications

NMR‐Guided Molecular Docking of a Protein–Peptide Complex Based on Ant Colony Optimization

NMR‐Guided Molecular Docking of a Protein–Peptide Complex Based on Ant Colony Optimization

The NMR2 Method to Determine Rapidly the Structure of the Binding Pocket of a Protein–Ligand Complex with High Accuracy

Opioids Bind to the Amino Acids 84 to 118 of UDP-Glucuronosyltransferase UGT2B7

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