NMR Spectroscopy
Magnetic Resonance Spectroscopy is an experimental technique utilized by chemists, structural biologists, and physicians. In this page, I list some programs (and their brief description) I have found useful. For a more complete listing of programs see: Protein NMR - A Practical Guide and NMR Wiki. In truth there are many great resources available online for NMR and this does not intend to replace any of these, but rather provide a list of programs I'm familar with.
Please feel free to email me with questions about how to use any of these programs or for any scripts I may have (will eventually post online).
Programs for calculating or analyzing three-dimensional structures:
- Xplor-NIH uses an energy function approach to calculate the three-dimensional structure of macromolecules.
- Cyana uses torsion angle dynamics to calculate the structure (rather than cartesian co-ordinates employed by Xplor-NIH, which makes Cyana much quicker than Xplor-NIH.
In addition to Cyana's speed superiority, it has an automatic NOE assign protocol, which can dramatically speed up the structure calculation (versus manually assigning all the NOEs prior to structure calculation). On the other hand, Cyana's limitation when compared with Xplor-NIH is its overly restrained structures. Another major problem with Cyana is that it is not trivial to solve protein-drug structures.
So a method I most often employed in my protein-ligand structure calculations was to use Cyana to first automatically assign the NOEs of the protein and then convert the NOE lists to Xplor-NIH format for the inclusion of NOEs made between the protein and the small molecule for a final refinement in Xplor-NIH. At this point, explicit solvent would also be used.
Other programs for calculating or analyzing three-dimensional structures:
- Talos+ is a program for the prediction of phi and psi angles for a protein based on a database of chemical shifts of proteins with crystal structures known.
- Smartnotebook is a program for the semi-autmoated assignment of the backbone of a protein.
- pjnmr is a program that aids in the understanding and/or coding of NMR pulse sequences by simulating the density matrix and vector diagrams of nuclei magnetization during an NMR experiment.
- interhlx is a program that calculates the angles between helices in a protein structure (or ensemble of structures).
- xcrvfit is a curve fitting tool designed for common NMR experiments, such as pH titrations, ligand titrations, relaxation experiments, etc.
- orbplus is a program that utilizes amide chemical shifts and a database of structures to predict tertiary structure of a protein.
Protein-drug structure calculation websites:
- PRODRG2 Server will convert a chemical structure into an energy minimized three-dimensional structure (in PDB format).
- Gaussian is a computational chemistry program. The structures calculated by this program are much more accurate than those estimated by PRODRG. Gaussian is not free, and if you have NMR data that provides information of the structure of the small molecule, then gaussian may not be necessary. If you plan to solve a structure of a protein-drug complex in explicit solvent (and therefore will be using electrostatic energy terms) Gaussian can accurately predict partial charges for the small molecule which will improve the accuracy of the structure calculation significantly.
- HIC-Up Server will take the PDB file for your small molecule (generated from either Gaussian or the PRODRG server to generate the necessary dictionaries for Xplor-NIH (i.e. the protein structure file (PSF)). The PSF contains information on the atom type, mass, partial charge, and connectivity.
Relaxation Software:
- Relax is a well maintained, GUI-based NMR relaxation analysis software package.
- Mathematica Notebooks from the laboratory of Dr. Leo Spyracopoulos
Solid-state NMR Software:
- Simpson is a program that simulates solid-state NMR spectra
Databases for structures or NMR data:
- The RCSB Protein Data Bank (PDB) is a database of protein structures.
- The Spectral Database (SDBS) for Organic Compounds is an excellent resource for searching for the chemical shifts of small molecules.
- Biological Magnetic Resonance Data Bank (BMRB) contains NMR data such as relaxation data and chemical shift assignments for macromolecules.
