SARomics Biostructures offers a broad range of custom protein NMR spectroscopy services for protein three-dimensional structure determination and compound library screening. Among our services are the following:
✓ 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
Please see below for details.
Protein NMR can be used as an alternative or as a complement to protein X-ray crystallography for the study of structure and dynamics. Although the resolution of the NMR data is normally lower than that of crystallographic data, structure determination by NMR spectroscopy still provides valuable information on the structure, its dynamics, ligand binding sites (ligand screening), etc. One obvious case is when a protein resists crystallization, but may still yield good-quality NMR spectra.
Which ligands in your panel bind to the target protein? Where in the protein is the binding site? What is the dissociation constant for a particular ligand? Protein NMR experiments offer convenient means of addressing these questions and many more.
Does your construct result in a folded, well-behaved protein? Protein NMR can provide a quick and reliable estimate 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.
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. Protein NMR spectroscopy is the only experimental technique available that enables atom-specific information of protonation equilibria in proteins.
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. Please see the list and practical considerations for the details of the NMR experiments.