protein NMR spectroscopy services

NMR Spectroscopy Services for Drug Discovery

We offer a broad range of biological NMR spectroscopy services:
• Protein structure determination in solution
• Binding assays/fragment screening
• Identification of flexible regions
• Verification of the structural integrity of target protein constructs
• pKa determination of titrating groups
• Validation of peptides and other low-molecular-weight compounds

Detailed description of our NMR services

High-resolution 3D structure determination in solution
As an alternative to X-ray crystallography, we use NMR spectroscopy to determine the structure and dynamics of proteins in solution. Proteins that fail to crystallize may be highly suitable for solution NMR studies. For example, highly flexible proteins often resist crystallization but may still yield high-quality NMR spectra.

Ligand binding assay and fragment screening
Which ligands in your panel bind to the target protein? Where in the protein is the binding site located? What is the dissociation constant for a particular ligand? NMR spectroscopy offers convenient means of addressing these questions and many more.

Verification of target constructs
Does your construct result in a folded, well-behaved protein? Protein NMR can provide a high-resolution picture of the physical state of a protein. The HSQC fingerprint spectrum readily shows whether the protein is well-folded, unfolded or ‘molten globule-like, and whether parts of the protein are flexible. This information is often very useful as a preparatory step before initiating crystallization trials.

pKa determination of titrating groups
Knowing the pKa values of residues in the vicinity of the binding/active site of a protein can be crucial for accurate modeling of the electrostatic interactions that contribute to ligand binding and consequently for computational optimization of designed ligands and in silico screening. NMR spectroscopy is the only experimental technique available that enables atom-specific information of protonation equilibria in proteins.

Validation of peptides and other low-molecular-weight compounds
Is the primary sequence of your peptidomimetic lead what you expect it to be? Does your peptide populate multiple conformations in solution? Which one is the active one? NMR spectroscopy is a very powerful tool for investigating these types of problems. We perform multi-dimensional (1H/1H, 1H/13C, or 1H/15N) NMR experiments as a basis for detailed structure analysis.

Practical considerations for NMR experiments are described in the technology pages.