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2D NMR: Includes COSY and NOESY.

3D NMR: See multidimensional NMR.

4D NMR: See multidimensional NMR.

atomic resolution data: Until the mid-1990's there were few reports extant of proteins that diffracted to resolutions better than 1.3 Å. With improvements in techniques for protein purification and the availability of third- generation synchrotron beamlines, atomic- resolution data collection on macromolecules has become much more common. These experiments provide exciting new insights into the structure and dynamics of macromolecules because they enable visualization of details inaccessible at lower resolution. [Industrial Macromolecular Crystallography Association, "Scientific Accomplishments of IMCA-CAT in 1999"] http://icarus.csrri.iit.edu/~ahoward/peb99/peb99science.html 

beamline: Beamlines at these storage rings, or synchrotrons, are the facilities at which crystallographers and other researchers get access to the tunable and high- intense X-ray beams they need for their research. [Introduction to the Professions, Illinois Institute of Technology, Sept. 26, 2000]    http://icarus.csrri.iit.edu/itp/itpmacro.html

Related terms synchrotrons; In-depth  Industrial Macromolecular Crystallography Association IMCA 

bicelle: [Nico] Tjandra & [Ad] Bax  recently developed a new nuclear magnetic resonance (NMR) technique that gently aligns protein molecules in a bath of liquid crystals, allowing researchers to determine how each bond between neighboring atoms is oriented with respect to the rest of the molecule. By compiling all such orientations between atoms, a precise map of the protein can be derived. In aqueous solution, just above room temperature, the lipids switch from a gel to a Liquid Crystal (LC) phase, where they form disc shaped particles, often referred to as bicelles. [Avanti Polar Lipids website]  http://www.avantilipids.com/BicellePreparation.asp

¹³C : Carbon isotopes used in NMR labeling.

ClogP: Algorithms & data management glossary In-depth

COSY: Correlated Spectroscopy, 2D NMR.

chemical shift: An atomic property that varies depending on the chemical and magnetic properties of an atom and its arrangement within a molecule. Chemical shifts are measured by NMR spectroscopists to identify the types of atoms in their samples. [NIGMS, US Structures of Life glossary, 2000 http://www.nigms.nih.gov/news/science_ed/structlife.pdf.

NMR Nomenclature: Nuclear Spin Properties and Conventions for Chemical Shifts IUPAC Provisional Recommendations, Physical and Biophysical Chemistry Division, Commission Molecular Structure and Spectroscopy Comments by Aug. 21, 2001 http://www.iupac.org/reports/provisional/abstract01/harris_310801.html

chemical shift anisotropy CSA: A “relaxation” property. [CHI Structural proteomics Report]

cryogenic probe: One of the engineering challenges has been to cool the detection circuitry to these very low temperatures while maintaining the sample itself at ambient temperatures.  The first generation of these cryoprobes provides a factor of three improvement in signal- to- noise ratio, which means about a factor of nine or ten reduction in data collection time.

Soon we will be able to combine the cryoprobes with the NOESY data collection and residual dipolar coupling to determine complete high- quality protein structures much faster. [CHI Structural proteomics Report] 

Related terms cryoprobe, microcryoprobes, triple resonance cryoprobes.

cryoprobe ™ : Bruker has developed  high- performance cryogenic probes for high- resolution applications. These probes have improved signal/noise (S/N) ratios obtained by reducing the operating temperature of the coil and the pre- amplifier. The dramatic increase in the S/N ratio by a factor of  4, as compared to conventional probes, leads to a possible reduction in experiment time of 16  or a reduction in required sample concentration by a factor of 4.  [Bruker website] http://www.bruker.de/analytic/nmr-dep/probes/cryoprobe.htm

Related terms cryogenic probe, microcryoprobes.

crystallography: The branch of science that deals with the geometric description of crystals and their internal arrangement. [OMD]  Narrower term X-ray crystallography.

Dalton: Unit of mass equal to the unified atomic mass (atomic mass  constant). [IUPAC Compendium] After John Dalton (1766-1844) British chemist and physicist.

dephases: (Electricity.) To put out of phase, as two parts of a single alternating  current. [dictionary.com]  http://www.dictionary.com/cgi-bin/dict.pl?term=dephase

deuterium- decoupled triple- resonance NMR: Gives an improvement in sensitivity.  If you randomly change some of the hydrogens in the sample to deuterium, then all of the other peaks in the spectrum can be made sharper, and the pulse sequence can be designed to erase, or decouple, the resonance- splitting effects of deuterium. [CHI Structural proteomics Report]

EPR Electron Paramagnetic resonance: See ESR.

ESR Electron Spin Resonance: ESR, often called Electron Paramagnetic Resonance (EPR), is similar to Nuclear Magnetic Resonance (NMR), the fundamental difference being that ESR is concerned with the magnetically induced splitting of electronic spin states, while NMR describes the splitting of nuclear spin states. In both ESR and NMR, the sample material is immersed in a strong static magnetic field and exposed to an orthogonal low- amplitude high- frequency field. ESR usually requires microwave- frequency radiation (GHz), while NMR is observed at lower radio frequencies (MHz). With ESR, energy is absorbed by the sample when the frequency of the radiation is appropriate to the energy difference between two states of the electrons in the sample, but only if the transition satisfies the appropriate selection rules. Splitting can occur only when the electron is in a state with non- zero total angular momentum, i.e. electrons in atoms with closed atomic shells cannot show this behavior. The term ESR refers specifically to the case in which the spins of the electrons absorbing the radiation are only weakly interacting ("weakly coupled") with each other. In NMR the static magnetic field splits the quantum states of a nucleus which has non- zero nuclear spin. The observation of NMR requires that the total electronic spin be zero. [Senior Physics Lab, California Institute of Technology, US, Sept. 2000] http://www.pma.caltech.edu/~ph77/labs/exp6.html

FT-NMR: Fourier Transform NMR: Fourier- transform NMR spectrometers use a pulse of radiofrequency (RF) radiation to cause nuclei in a magnetic field to flip into the higher- energy alignment. Due to the Heisenberg uncertainty principle, the frequency width of the RF pulse (typically 1-10 µs) is wide enough to simultaneously excite nuclei in all local environments. All of the nuclei will re- emit RF radiation at their respective resonance frequencies, creating an interference pattern in the resulting RF emission versus time, known as a free- induction decay (FID). The frequencies are extracted from the FID by a Fourier transform of the time- based data.  [Juhyoun Kwak, Chemistry, KAIST, Korea Institute of Advanced Science & Technology]    http://elchem.kaist.ac.kr/vt/chem-ed/spec/spin/ftnmr.htm

flexible linkages: In proteins.

free induction decay FID: See spin; FT-NMR In-depth.

four-D See 4D

¹H: Hydrogen isotope used in NMR labeling.

HMQC Heteronuclear Multiple Quantum Correlation: Much of protein NMR spectroscopy relies on spectral editing techniques using ¹³C or ¹⁵N nuclei (heteronuclei). Spectral editing allows a subset of an entire spectrum to be observed. Normally, we observe a subset of ¹H spectra that has been selected based upon which nucleus the protons are attached to. The same techniques involved in spectral editing allow the measurement of heteronuclear correlations (which, for example, allows you to know which ¹H are attached to which ¹³C). [Arthur S. Edison, University of Florida, “Theory and Applications of NMR Spectroscopy, April 2000] http://ascaris.health.ufl.edu/classes/bch6746/new/html/note5.html

hr-MAS High Resolution Magic Angle Spinning: The sample is spun at a high speed at a well-defined angle to the main magnetic field. Orienting the sample in this manner is a technique that was developed originally for solid state NMR to minimize the spectral line broadening introduced by intermolecular dipolar coupling or sample inhomogeneity. The appeal of hr-MAS is that it allows the study of systems that were previously not accessible with NMR. Some particularly interesting recent applications of this technology include the study of biological tissues and combinatorial chemistry samples that have been isolated on polymer beads.  [Aileen Constans "Taking It Higher: State- of- the- Art NMR technology offers answers for the solution and solid states" Scientist 14 (21): 26, Oct. 30, 2000]  Broader term MAS Magic Angle Spinning  http://www.the-scientist.com/yr2000/oct/profile1_001030.html

HSQC Heteronuclear single quantum correlation: When a molecule binds a protein, the chemical environment of the protein’s binding site changes and results in the chemical shift perturbation of nuclei at that site. Two- dimensional ¹H -¹⁵N heteronuclear single- quantum correlation  (HSQC)- NMR spectroscopy screens for ligand binding by detecting only the amide signals of ¹⁵N- labeled protein. [Jennifer B. Miller, “Why NMR is attracting drug designers”  Today’s Chemist at Work 9 (1) : 44-49  Jan. 2000]   http://pubs.acs.org/hotartcl/tcaw/00/jan/miller.html

high-field NMR: The spectra of complex biomolecules contain a large number of peaks, many of which are close together or overlap. Higher field magnets, or higher frequency instruments, offer better peak resolution, enabling analysis of larger and larger molecules. Also, in NMR, sensitivity increases almost with the square of the magnetic field, so when magnetic field strength is doubled, sensitivity increases about fourfold. Data can thus be acquired faster, or alternatively, samples can be run at lower concentrations in the same experimental time. The latter advantage is particularly important to the study of large biomolecules, which are often difficult to express and purify in large quantities and can aggregate and precipitate out of solution at high concentrations. Finally, high- field NMR can lead to the development of new NMR experiments that exploit properties exhibited by molecules at high magnetic fields.  [Aileen Constans "Taking It Higher: State- of- the- Art NMR technology offers answers for the solution and solid states" Scientist 14 (21): 26, Oct. 30, 2000]  http://www.the-scientist.com/yr2000/oct/profile1_001030.html

high-resolution diffusion-ordered spectroscopy HR-DOSY: Philip Hodge and Gareth Morris and their colleagues at the University of Manchester [are] using NMR to help them pick out the best host molecules from an array of hopefuls for use in analytical sensor applications. ... A multi- dimensional version of NMR, which disperses signals for the members of the library according to an additional criterion: their diffusion coefficients. Normally all the members will diffuse relatively rapidly. However, when a soluble polymer, with an added side-group of interest, is added to the combinatorial array, each member of the array that binds to the functionality on the polymer diffuses more slowly than before. The magnitude of the shift indicates the strength of the interaction. The spectrum of the most tightly bound molecule can then be plotted.  [Elemental Discoveries Mar. 2001, Issue 39] http://www.sciencebase.com/mar01iss.html

hyphenated techniques: NMR together with chromatography and/ or mass spectrometry. Includes LC- NMR.

Industrial Macromolecular Crystallography Association IMCA:  Academic  crystallographers generally determine unknown structures; industrial crystallographers spend the majority of their time examining structures of complexes between a protein of known structure and a small- molecule ligand. These structures can be studied by difference Fourier methods, and are therefore simpler to execute and faster to complete than de novo structure determinations. ... The result of these difficulties is that pharmaceutical crystallographers began, in the mid- 1980's, to search for a venue of their own to pursue their goals. ... Keith Watenpaugh of Upjohn and Noel Jones of Eli Lilly & Co. recognized that a single corporation was unlikely to make the financial commitment necessary for building a dedicated industrial beamline at a major facility, whereas a consortium involving several corporations could make such a commitment. They discussed this concept with colleagues at other large pharmaceutical and chemical companies, and formed the Industrial Macromolecular Crystallography Association (IMCA) to pursue the goal of a pharmaceutical beamline at a storage ring. They chose the Advanced Photon Source at Argonne National Laboratory as the site for their facility, since the APS was then under construction and promised the highest brilliance and the best opportunity for developing specialized beamlines. In 1992 IMCA contracted with Illinois Institute of Technology to build and operate the IMCA beamlines at the APS. [Andrew. Howard "Participation of Pharmaceutical Companies in Synchrotron Radiation Research" Illinois Institute of Technology, June 1998] http://icarus.csrri.iit.edu/~ahoward/pharm_sr.html

Related terms beamline, synchrotrons.

isotope: A form of a chemical element that contains the same number of protons but a different number of neutrons than other forms of the element. Isotopes are often used to trace atoms or molecules  in a metabolic pathway. In NMR, only one isotope of each element contains the correct magnetic properties to be useful.  [NIGMS, US Structures of Life glossary, 2000 http://www.nigms.nih.gov/news/science_ed/structlife.pdf.

J coupling: See spin-spin coupling.

kD: kilo Dalton. Also abbreviated kDa.

LC-NMR: Liquid Chromatography - Nuclear Magnetic Resonance: Nuclear Magnetic Resonance spectroscopy (NMR) is a powerful analytical tool that can provide unambiguous structural information for small molecules. NMR, however, generally requires relatively high purity samples. Complex mixtures can give distorted and overlapping resonances making identification difficult. Furthermore, NMR detection is a relatively insensitive technique requiring substantial quantities of a particular analyte. The coupling of conventional HPLC [High Performance Liquid Chromatography] and NMR allows for detection and structural analysis of analytes in complex samples and is becoming an important mainstay in industry. [Wayne Kelley, Michael Lacey, "Hyphenation of Microscale HPLC and Microcoil NMR", Univ. of Illinois Urbana- Champaign 2000] http://mrel.beckman.uiuc.edu/sweedler/lc-nmr.htm

labels: See spin labels.

MAD Multiple Anomalous Dispersion: Multiple and single anomalous dispersion measurements are becoming increasingly popular as a method to solve protein structures. The possibility of obtaining completely unbiased phases at any resolution makes these methods intrinsically more reliable and robust than any other phasing technique used currently. [Ana Gonzalez, Staff Scientist, EMBL Research Station, Hamburg, Germany] http://www-db.embl-heidelberg.de:4321/emblGroups/g_81.html

MAD Multi-wavelength Anomalous Diffraction: A technique used in X-ray crystallography that accelerates the determination of protein structures. It uses X-rays of different wavelengths, relieving crystallographers from having to make several different metal- containing crystals.  [NIGMS, US Structures of Life glossary, 2000 http://www.nigms.nih.gov/news/science_ed/structlife.pdf

MAS Magic Angle Spinning: NMR strategy in which the tube is rotated at very high speed and at a  specific angle which cancels out the line broadening effects of inhomogeneities in the sample. This yields high resolution and high sensitivity which are very useful in trace analysis or in looking at solid phase synthesis resins. [IUPAC Combinatorial Chemistry]

Has since long been proven powerful in the studies of heterogeneous samples such as powdered solids, compartmentalized liquid samples, or heterogeneous solid- liquid mixtures. Recently it has been shown that higher resolution could be achieved if high- resolution  magnetic-  susceptibility- matching probe (Nano.nmr probe) technology was used in conjunction to MAS High resolution liquid NMR and magic angle spinning. [M. Delepierre ,”High Resolution Liquid NMR and Magic Angle Spinning” J. Chim. Phys., Vol. 95 (2) February 1998]  http://www.edpsciences.org/articles/jcp/abs/1998/02/dele/dele.html

Narrower term: hrMAS

MicroCryo Probes™ : Bruker offers these for 3 mm sample tubes. Traditionally, NMR samples are placed in 5 mm tubes, with a high solvent- to- sample ratio. With the increased sensitivity offered by accessories such as the CryoProbes, researchers have noticed more solvent impurities in their spectra. The 3 mm tubes and MicroCryoProbes allow spectroscopists to study mass- limited samples, such as natural products and metabolites, in less solvent.  [Aileen Constans "Taking It Higher: State-of-the-Art NMR technology offers answers for the solution and solid states" Scientist 14 (21): 26, Oct. 30, 2000] See also cryogenic probes, cryoprobe. http://www.the-scientist.com/yr2000/oct/profile1_001030.html

Based on cryogenically cooled receiver coils and electronics ... can make routine measurements in the nanogram range [Bruker website] http://www.bruker.com/nmr/AboutUs/Pdf_files/microcryoprobe.pdf.

mmCIF dictionary Macromolecular Crystallographic Information File: IUCF's [International Union of Crystallography] preferred archive file format for macromolecular data and structural reports. http://www.iucr.ac.uk/iucr-top/cif/mmcif/ndb/background/index.html

mmCIF Dictionary website, Rutgers Univ. US  http://ndbserver.rutgers.edu/mmcif/dictionary/

multidimensional (three- and four-dimensional) NMR: Introduced about 12-15 years ago. This technology has the advantage of resolving the severe overlap in 2D spectra and represents a very important breakthrough. [CHI Structural proteomics Report] Related terms 3D NMR, 4D NMR

¹⁵N: Nitrogen isotope label for NMR.

NMR Nuclear Magnetic Resonance:  NMR spectroscopy makes it possible to discriminate nuclei, typically protons, in different chemical environments. The electron distribution gives rise to a chemical shift of the resonance frequency. The chemical shift, , of a nucleus is expressed in parts per million (ppm) by its frequency, n, relative to a standard, ref, and defined as = 106 (n - ref)/o, where o is the operating frequency of the spectrometer. It is an indication of the chemical state of the group containing the nucleus. More information is derived from the spin- spin couplings between nuclei, which give rise to multiplet patterns. Greater detail may be derived from two- or three- dimensional techniques. These use pulses of radiation at different nuclear frequencies, after which the response of the spin system is recorded as a free- induction decay (FID). Multi- dimensional techniques, such as COSY and NOESY, make it possible to deduce the structure of a relatively complex molecule such as a small protein (molecular weight up to 25 000). In proteins containing paramagnetic centres, nuclear hyperfine interactions can give rise to relatively large shifts of resonant frequencies known as contact and pseudo- contact (dipolar) shifts, and considerable increases in the nuclear spin relaxation rates. From this type of measurement, structural information can be obtained about the paramagnetic site. [IUPAC Bioinorganic]

A technology for protein structure determination. NMR generally gives a lower- resolution structure than X-ray crystallography does, but it does not require crystallization. NMR is currently applicable only to smaller proteins. [CHI Structural proteomics Report]

In the last few years the role of Nuclear Magnetic Resonance (NMR) in both pharmaceutical and academic research has evolved dramatically. NMR has long been a powerful tool for characterizing protein structures. However, recent breakthroughs in NMR pulse methods and molecular alignment techniques have extended the size of systems to be studied and the accuracy with which structures can be determined. In pharmaceutical research, NMR screening of libraries and rational design of high- affinity ligands are now a main focus of numerous preclinical discovery efforts. NMR methods and instrumentation are being developed rapidly as groups seek high- throughput, low- cost approaches to accelerating the drug discovery process. Such approaches will be necessary as scientists attempt to characterize the large number of proteins currently being generated by structural genomics initiatives. NMR: Drug Discovery and Design — Post-Genomic Analysis Oct. 24-26, 2000

Narrower terms include 2D NMR, 3D NMR, 4D NMR, COSY, deuterium decoupled triple resonance NMR, high field NMR, LC-NMR, multidimensional NMR, NMR - biomolecular, NOESY, ROESY, reduced dimensionality triple resonance NMR, SAR by NMR, STD NMR, solid state NMR, solution state NMR, TOCSY, TROSY. In-depth FT-NMR Fourier Transform NMR triple resonance NMR. Related term ESR Electron Spin Resonance

Spectroscopy Now, NMR Knowledge Base, John Wiley & Sons, Ltd., UK  http://www.spectroscopynow.com/Spy/basehtml/SpyH/1,9076,5-0-0-0-0-home-0-0,00.html

NMR active atom: An atom that has the correct magnetic properties to be useful for NMR. For some atoms, the NMR-active form is a rare isotope, such as ¹³C or ¹⁵N. [NIGMS, US Structures of Life glossary, 2000 http://www.nigms.nih.gov/news/science_ed/structlife.pdf

NMR Nuclear Magnetic Resonance - biomolecular: NMR spectroscopy on small- to medium- size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope. [MeSH]

NMR spin relaxation spectroscopy: A powerful experimental approach for globally characterizing conformational dynamics of proteins in solution. Laboratory frame relaxation measurements are sensitive to overall rotational diffusion and internal motions on picosecond- nanosecond time scales, while rotating frame relaxation measurements are sensitive to chemical exchange processes on microsecond- millisecond time scales. [Arthur G. Palmer III "NMR investigations of Protein Motions and Folding" Vanderbilt Biomolecular NMR Symposium, Oct. 6, 2001] http://structbio.vanderbilt.edu/nmr/symposium/abstracts.phtml

NOE Nuclear Overhauser Effect: The interaction between the dipole moments of two nuclei in spatial proximity, provides information about the distance between nuclei and is one of the parameters studied in multidimensional  NMR.  [Aileen Constans "Taking It Higher: State- of- the- Art NMR technology offers answers for the solution and solid states" Scientist 14 (21): 26, Oct. 30, 2000]  http://www.the-scientist.com/yr2000/oct/profile1_001030.html  

The Nuclear Overhauser Effect is a tremendously powerful tool for examining spatial relationships in molecular systems. The effect is characterized by a transfer of polarization (spins) from one nucleus to another through space (not through bonds). The distance dependence of the NOE is r6 so only short range interactions are ever seen. [Ted Bartlett, Joel Gohdes,  Fourier Transform NMR Lab Manual, Chem 454, Ft. Lewis College, US, Fall 2000]  http://faculty.fortlewis.edu/gohdes_J/c454f00lm.html

Related term NOESY

NOESY  Nuclear Overhauser Effect (NOE)  SpectroscopY: An NMR technique used to help determine protein structures. It reveals how close different protons (hydrogen nuclei) are to each other in space.  [NIGMS, US Structures of Life glossary, 2000 http://www.nigms.nih.gov/news/science_ed/structlife.pdf

NOESY, ROESY and TROESY: what is the difference? FAQ 98-08.1 
http://nmr.chem.ualberta.ca/AOWWW/nmr_news/98-08.htm#FAQ  [NMR FAQ, Chemistry Dept. Univ. of Alberta, Canada]

NOESY spectra: Allow the space interactions between atoms to be measured and generate a 3D structure of the protein. [CHI Structural proteomics Report]

pulse sequence: The application of a set of radio frequencies to a sample to produce a specific form of an NMR signal.  Many different types of pulse sequences have been designed for modulating the NMR signal; pulse sequences allow the optimization of the NMR signal for the study of different types of samples. The result is a sharpening of all the peaks and a significant improvement their signal- to- noise ratios and their value for structural analysis. [CHI Structural proteomics Report]

pulsed field gradients PFG: Indicating that a probe is capable of doing gradient-enhanced spectroscopy. [Glossary, AO-VNMR, Univ. of Alberta, Canada] >http://nmr.chem.ualberta.ca/AOWWW/glossary.htm

ROESY: Rotating frame Overhauser Enhancement SpectroscopY

reduced dimensionality triple resonance NMR: Being pioneered by people like Professor Thomas Szyperski at the State University of New York in Buffalo to exploit the higher sensitivity of cryogenic probes.  [CHI Structural proteomics Report] Related term In-depth triple resonance NMR

relaxation: Passage of an excited or otherwise perturbed system towards or into thermal equilibrium with its environment.  [IUPAC Photochemistry]

If a system is disturbed from its state of equilibrium it relaxes to that state, and the process is referred to as relaxation. The branch of kinetics concerned with such processes is known as relaxation kinetics. Relaxation techniques include temperature jump and pressure jump. See also chemical relaxation.  [IUPAC Compendium] 

residual dipolar coupling: A relatively new way to measure relative orientations of bonds with respect to one another.  In NMR structure determination, distances are measured between atoms and interatomic distances are converted into 3D structures.  Now relative orientations of bonds can also be measured to give many more constraints, allowing structures to be determined more precisely, or being able to deal with larger proteins.  [CHI Structural proteomics Report]

resonance assignments: An early step in the process of NMR- based structure determination can be done rapidly for proteins up to approximately 30 kDa.  Although resonance assignments do not provide the complete structure of a protein, they often provide important structural information about a protein’s binding site, which can then be used to determine function. [CHI Structural proteomics Report]

SAR by NMR Structure Activity Relationship by Nuclear Magnetic Resonance: Developed by Stephen Fesik of Abbott Laboratories. Allows the rapid screening and evaluation of thousands of compounds against a target protein. This screening technology detects whether a compound interacts by binding to the target protein, and it may also identify the binding epitope on the target. Different compounds may bind to adjacent, but different, sites. The next step in the SAR by NMR approach is to create structure- based- designed chemical libraries that link fragments of the original hits to yield high-potency leads. This method, however, requires a complete sequence- specific resonance assignment of the NMR- spectrum, which is still a time- consuming effort. [CHI Structural proteomics Report]

STD-NMR Saturation Transfer Difference NMR: The difference of a saturation transfer and a normal NMR spectrum provides a new and fast method (STD NMR) to screen compound libraries for binding activity to proteins. STD NMR of mixtures of potential ligands with as little as 1 nmol of protein yields 1D and 2D NMR spectra that exclusively show signals from molecules with binding affinity. In addition, the ligand´s binding epitope is easily identified because ligand residues in direct contact to the protein show much stronger signals, e.g. the binding specificity of  Lewisb- hexasaccharide to Aleuria aurantia agglutinin (AAA) can be mapped to the two fucosyl residues. [Characterization of Ligand Binding by Saturation Transfer Difference NMR Spectra,  M. Mayer, B. Meyer, Angew. Chem. Int. Ed., 1999, 35, 1784-1788] http://sgi1.chemie.uni-hamburg.de/cgi-bin/abstracts.cgi?filename=pub29.html

single cell NMR imaging: Spatial and temporal molecular species maps of intact single cells will be needed by biologists in the future. The development of single cell NMR imaging is thus particularly important for characterization of non- protein signaling elements within the cell.   [National Center for Research Resources "Integrated Genomics Technologies Workshop Report" Jan 1999]  http://www.ncrr.nih.gov/newspub/genomic.pdf 

site-directed NMR analysis: Understanding how ligands bind to a protein target is an essential part of drug development. Binding characteristics help determine how well the drug works - how effective and selective it is, and whether it can be administered in reasonable quantities. Traditionally, protein- ligand binding has been studied using X-ray crystallography (co- crystallography). But this approach can be  time- consuming and does not allow researchers to see how the drug works in solution.  Now it is becoming more common to use NMR for studies of ligand- binding conformations (i.e., a small molecule bound to a protein target). [CHI Structural proteomics Report] Related term site-specific screening.

site-specific screening: Researchers at the new Pharmacia spin- off, Biovitrum, also use NMR for structure- based, site- specific screening.  Conceived of by Mats Wikstrom, head of macromolecular structures at Biovitrum, this method uses site- specific isotopic labeling of two amino acid residues, a technique described by Masatune  Kainosho (Tokyo Metropolitan University) ...  In this approach, two amino acid types are labeled with ¹³C and ¹⁵N.  If this pair of amino acids occurs only once in the sequence, there will be only one peak in a one- dimensional/ two- dimensional HNCO- type NMR spectrum. This technique allows researchers to screen for only those binders that interact with a specific site of the receptor.  [CHI Structural proteomics Report] Also referred to as site- directed NMR.

solid state NMR: Requires wider- bore (63 or even 89 mm diameter) magnets [than solution state NMR]. The higher stored energy of  these wide bore magnets means that they are significantly more difficult to build, and as a result high- field solid state NMR lags behind liquid state in terms of available field strength. The highest field currently available for a wide bore magnet is 800 MHz .  [Aileen Constans "Taking It Higher: State- of- the- Art NMR technology offers answers for the solution and solid states" Scientist 14 (21): 26, Oct. 30, 2000]  http://www.the-scientist.com/yr2000/oct/profile1_001030.html

Can be used to study proteins that cannot be crystallized or are too large for  solution state NMR methods.

solution state NMR: NMR in liquids

spin: The nuclei of certain atoms, for example, ¹H, ¹³C, and ¹⁵N, exhibit a physical property known as spin. These nuclei can be viewed as tiny magnets that, when placed in an external magnetic field, can orient themselves in two possible ways, with spin vectors aligned in the direction of, or directly against, the field. For nuclei with a nuclear quantum spin number of 1/2, such as those listed above, these two orientations correspond, respectively, to a low energy state and a high- energy state. Transitions between the two states occur spontaneously, but infrequently. However, if the sample is irradiated with energy equivalent to the energy difference between the two states - in the radio frequency, or RF, range - transitions will occur more frequently. These induced transitions form the basis of NMR spectroscopy. When the magnetization vectors associated with the transitions are rotated perpendicular to the applied field, they precess about the direction of the field and induce a current in the receiver coil, which is recorded and plotted as a function of time. The resulting sine wave decays with time due to spin dephasing, and the signal is recorded as a free induction decay (FID), which is then converted into a frequency domain spectrum.  [Aileen Constans "Taking It Higher: State- of- the- Art NMR technology offers answers for the solution and solid states" Scientist 14 (21): 26, Oct. 30, 2000] http://www.the-scientist.com/yr2000/oct/profile1_001030.html  Related terms spin labels, spin probes, spin properties, spin- spin coupling, spin- spin relaxation.

spin labels: A stable paramagnetic group that is attached to a part of another molecular entity whose microscopic environment is of interest and may be revealed by the electron paramagnetic resonance spectrum of the spin label. When a simple paramagnetic molecular entity is used in this way without covalent attachment to the molecular entity of interest it is frequently referred to as a "spin probe". [IUPAC Bioinorganic] See also ¹H,  ¹³C, ¹⁵N.

spin probe: See under spin label.

spin properties: IUPAC Provisional Recommendations: NMR Nomenclature: Nuclear Spin Properties and Conventions for Chemical Shifts, Physical and Biophysical Chemistry Division, Commission Molecular Structure and Spectroscopy Comments by Aug. 21, 2001 http://www.iupac.org/reports/provisional/abstract01/harris_310801.html

spin-spin coupling: The interaction between the spin magnetic moments of different electrons and/or nuclei. In NMR spectroscopy it gives rise to multiplet patterns, and cross- peaks in two- dimensional NMR spectra. Between electron and nuclear spins this is termed the nuclear hyperfine interaction. Between electron spins it gives rise to relaxation effects and splitting of the EPR spectrum. [IUPAC Bioinorganic]

Is this the same as J coupling ?

spin-spin relaxation: A solid- state physics process involving raising temperatures using weak magnetic fields.

storage rings: See under beamline, synchrotrons.

synchrotrons: Devices for accelerating protons or electrons in closed orbits where the accelerating voltage and magnetic field strength varies (the accelerating voltage is held constant for electrons) in order to keep the orbit radius constant. [MeSH]

A large machine that acceleratees electrically charged particles to nearly the speed of light and maintains them in circulat orbits. Originally designed for use by high- energy physicists, synchrotrons are now heavily used by structural biologists as a source of very intense X- rays.  [NIGMS, US Structures of Life glossary, 2000 http://www.nigms.nih.gov/news/science_ed/structlife.pdf

A key development in the high throughput crystallographic solving of protein structures, shortening X-ray diffraction data collection time from days to hours and reducing the size of crystals needed to produce useful data. [Terry Gaasterland “Structural genomics: Bioinformatics in the driver’s seat” Nature Biotechnology 16:625-627 July 1998]

Related terms beamline; Industrial Macromolecular Crystallography Association IMCA; nanoscience Miniaturization glossary

Synchrotron X-ray sources in the world, ESRF European Synchrotron Radiation Facility, Grenoble, France.   http://www.esrf.fr/navigate/synchrotrons.html

TOCSY: TOtal Correlation SpectroscopY

TROESY: Transverse Rotating Frame Overhauser Effect Spectroscopy. 

TROSY Transverse Relaxation Optimized Spectroscopy: Invented about 1997. First described by Professor Kurt Wuthrich. Useful for analyzing larger protein systems. TROSY is a method for getting sharper peaks on large proteins.

TROSY is best at higher fields. If the aim is to study a large complex or a chemical shift perturbation when a protein binds to a receptor using NMR, it’s better to use a 900 MHz machine than a more standard lower- field machine. [CHI Structural proteomics Report]

three-D See 3D

triple-resonance cryoprobes: By using a triple- resonance cryoprobe, we can collect in six hours the same data which required over two weeks of data- collection time with a conventional probe. [CHI Structural proteomics Report]

triple-resonance NMR: Introduced in 1989, involves isotope labeling with ¹⁵N and ¹³C. (N = nitrogen; C = carbon.). Methods and software for automated analysis of now becoming available. [CHI Structural proteomics Report]

two-D See 2D

X-ray crystallography: The most widely used (and most accurate) method of obtaining structures, X-ray crystallography involves expressing highly purified protein samples, crystallizing these, and then performing X-ray diffraction of the protein to elucidate crystal structure.  Computational software is then used (combined with extensive - but increasingly less - human judgment) to convert X-ray diffraction data into high- resolution structures. Note that many proteins cannot be crystallized at present. [CHI Structural proteomics Report]  Related term synchrotrons.

X-ray diffraction: <investigation> Basis of powerful technique for determining the three dimensional structure of molecules, including complex biological macromolecules such as proteins and nucleic acids, that form crystals or regular fibres. Low angle X-ray diffraction is also used to investigate higher levels of ordered structure, as found in muscle fibres.  [OMD 18 Nov 1997] 

Bibliography

AO-VNMR Glossary, Albin Otter, Chemistry Dept. Univ. of Alberta, Canada, 2001.  http://nmr.chem.ualberta.ca/AOWWW/  About 50 terms.

Basics of NMR: Glossary,  J.P. Hornak, Rochester Institute of Technology, US 1997-1999 http://www.cis.rit.edu/htbooks/nmr/inside.htm

CCMC Crystallography Made Crystal Clear, Gale Rhodes, Chemistry Dept., Univ. of Southern Maine, US http://www.usm.maine.edu/~rhodes/CMCC/index.html  Web resource for print Crystallography Made Crystal Clear (2nd ed.)

[CHI Structural Proteomics: High-Throughput Approaches Fuel Drug Discovery and Development, Cambridge Healthtech Institute report, Malorye Branca, Allan Haberman, Deidre Lockwood,  2001  

Elves Manual Glossary of X-ray Terms, James Holton, Univ. of California Berkeley, US http://ucxray.berkeley.edu/~jamesh/elves/manual/basics.html

IUPAC Recommendations for the Presentation of NMR Structures of Proteins and Nucleic Acids, John L Markley et. al. July 28, 1998  http://www.bmrb.wisc.edu/home/iupac.pdf

IUPAC Provisional Recommendations: NMR Nomenclature: Nuclear Spin Properties and Conventions for Chemical Shifts, Physical and Biophysical Chemistry Division, Commission Molecular Structure and Spectroscopy Comments by Aug. 21, 2001 http://www.iupac.org/reports/provisional/abstract01/harris_310801.html

Judging the Quality of Macromolecular models Glossary of Terms from Crystallography, NMR and Homology Modeling :Gale Rhodes, Chemistry Dept. Univ. of Southern Maine, US, 2000 http://www.usm.maine.edu/~rhodes/ModQual/index.html

Statistical descriptors in Crystallography, Glossary of statistical terms, International Union of Crystallography, 1996 http://www.iucr.org/iucr-top/comm/cnom/statdes/index.html#gloss

Virtual Library: Crystallography, International Union of Crystallography http://www.ch.iucr.org/cww-top/int.w3vlc.html

Alpha glossary index

IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.