We offer a broad range of services using nuclear magnetic resonance (NMR) spectroscopy for protein structure determination:
• 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
• FastLane™ Premium structures
• FastLane™ Standard Structures
• Antibody-Antigen Complexes
• Biosimilars Quality Validation
• Integrated Lead Discovery
• Fragment Library Screening
• In silico Lead Discovery Services
• ProPHECY™ - in silico Peptide and Protein Optimization
High-resolution 3D structure determination in solution
In structural biology, as an alternative to protein structure determination by X-ray crystallography, it is possible to use NMR spectroscopy to study protein structure and dynamics in solution. Although the resolution of the NMR data is normally lower than that of X-ray crystallographic data, structure determination by NMR spectroscopy my still provide valuable information on the structure, its dynamics, ligand binding sites (ligand screening), etc. One obvious case is when a highly flexible protein resists 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 experiments offer 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 amino acid residues in the vicinity of the binding/active site of a biological macromolecule 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.
We have access to state-of-the art NMR spectrometers. See the list and practical considerations for the details of the NMR experiments.