Nuclear magnetic resonance (NMR) spectroscopy uses high magnetic fields and radio- frequency pulses to manipulate the spin states of nuclei — including 1H, 13C, and 15N — that have nonzero- spin angular momentum. For a molecule containing such nuclei, the result is an NMR spectrum with peaks whose positions and intensities reflect the chemical environment and nucleic positions within the molecule. As applied to protein- structure analysis, the accuracy now achievable with NMR spectroscopy is comparable to that obtained with X-ray crystallography. Nuclear Magnetic Resonance Spectroscopy, DOE Genomes to Life, US  http://www.doegenomestolife.org/technology/nmrspectroscopy.html

Technologies map   Finding guide to terms in these glossaries   Site Map
Related glossaries include Protein Structures, Structural Genomics

2D NMR: Includes COSY and NOESY.

3D NMR: See multidimensional NMR.

4D NMR: See multidimensional NMR.

beamline: In particle physics, a beamline is the line along which a beam of particles travels through, or when projected from, a particle accelerator. It may refer to the line of travel within an actual accelerator, and to the equipment that maintains that beam in a storage ring or accelerates it in a linear accelerator. It may also refer to a beam of X-rays projected to stations for doing crystallography  Beamline, Wikipedia, accessed Oct. 3, 2005

Google = about 240,000  June 7, 2004, about 1,210,000 Oct. 3, 2005

Related terms: synchrotrons, 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

COSY: Correlated Spectroscopy, 2D NMR.

chemical shift: The variation of the resonance frequency of a nucleus in nuclear magnetic resonance (NMR) spectroscopy in consequence of its magnetic environment. The chemical shift of a nucleus, is expressed in ppm by its frequency, cpd, relative to a standard, ref, and defined as = 106(cpd - ref)/o  where o is the operating frequency of the spectrometer. For ¹H and ¹³C NMR the reference signal is usually that of tetramethylsilane (SiMe4). Other references are used in the older literature and in other solvents, such as D2O.  If a resonance signal occurs at lower frequency or higher applied field than an arbitrarily selected reference signal, it is said to be upfield, and if resonance occurs at higher frequency or lower applied field, the signal is downfield. Resonance lines upfield from SiMe4 have positive, and resonance lines downfield from SiMe4 have negative -values. [IUPAC  Physical Organic Chemistry]

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.

Google = about 68, 200 June 7, 2004

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. 

comparative spectral analysis CoSA: SEE under Quantitative ¹³C NMR Spectrometric Data- Activity Relationships Modeling QSDAR

comparative structural connectivity spectra analysis CoSCSA: SEE under Quantitative ¹³C NMR Spectrometric Data- Activity Relationships Modeling QSDAR

comparative structurally assigned spectral analysis CoSASA: SEE under Quantitative ¹³C NMR Spectrometric Data- Activity Relationships Modeling QSDAR 

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. 

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.

crystal: A regular repeat of molecules, usually with some sort of internal rotational symmetry. Protein crystals are usually about 40- 60% solvent by weight and are thus fragile and sensitive to drying out. [Robert L. Campbell, Protein crystallography: Important points and definitions. Dept. of Biophysics and Biochemistry, Johns Hopkins Univ., US http://biophysics.med.jhu.edu/rlc/lect/definitions.html

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

The study of the structures of molecules contained within crystals. A crystal is a solid that consists of millions of virtually identical tiny repeating units called "unit cells"; each unit cell is the same size, is oriented identically, and has the same contents, as every other unit cell. Typically the unit cell contains one or a small number of molecules. IMCA- CAT: A Layman's Introduction http://www.imca.aps.anl.gov/ 

Narrower terms: X-ray crystallography, synchrotron- based x-ray crystallography

crystallomics: -Omes & -omics

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. 

EMR Electron Magnetic Resonance: See under ESR

EPR Electron Paramagnetic resonance: See under ESR.

ESR Electron Spin Resonance: Electron paramagnetic resonance (EPR) and electron spin resonance (ESR) can be viewed as two alternative names in a family of electron magnetic resonance (EMR) techniques. The measurements owe their origin to the magnetic properties of the electron which, since it has a magnetic moment (associated with the electron spin), will interact with an external magnetic field. Simply, the electron can behave like a small bar magnet when placed in a magnetic field, trying to align itself with the external field. It is then possible to cause the electron to 'flip' from alignment with the external field, to alignment against the field by irradiation with suitable microwave electromagnetic radiation. (Gigahertz, that is 10⁹Hz). Resonance techniques are generally used to measure this intriguing phenomenon, with the measurements finding uses in science topics as diverse as anthropology, the brewing industry, metalloenzyme biochemistry and the study of the electronic properties of molecules and atoms, Like its younger cousin, NMR, nuclear magnetic resonance, EMR is also developing as an imaging technique for magnetic resonance imaging (MRI).  ESR Electron Spin Resonance Group of the Royal Society of Chemistry, What's in a name? http://www.esr-group.org.uk/Name.html 

EMR Abbreviations http://www.esr-group.org.uk/Name.html#abbrev 

FT-NMR: Fourier Transform NMR: A major breakthrough occurred in 1966. Richard R. Ernst then discovered (together with Weston A. Anderson, USA) that the sensitivity of NMR spectra could be increased dramatically if the slow frequency sweep was replaced by short, intense radiofrequency pulses. The pulses cause a signal to be emitted by the nuclei. This signal is measured as a function of time after the pulse. It cannot be interpreted directly. Ernst discovered, however, that it was possible to extract the resonance frequencies from such a signal and to convert the signal into a NMR spectrum by a mathematical operation (Fourier* transformation, FT). This is performed rapidly in a computer. The whole process can be compared with stretching both arms over a piano and pushing all the keys at the same time. All the tones are there, but they are difficult to distinguish. A computer can discern the different tones (frequencies). Ernst's discovery is the basis of modern NMR spectroscopy, called FT NMR. It leads to a tenfold, and sometimes 100-fold increase in sensitivity since the pulse response contains information on all resonance frequencies at the same time. [Fourier-Transform NMR, Nobel e-Museum, 2001] http://www.nobel.se/chemistry/educational/poster/1991/fourier.html

flexible linkages: In proteins.

fluxome: Omes & omics

free induction decay FID: See spin, FT-NMR 

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]  http://www.the-scientist.com/yr2000/oct/profile1_001030.html

Broader term: MAS Magic Angle Spinning 

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 pressure NMR: Pressure is a thermodynamic variable of interest for protein structural and functional studies because of its importance to the standard volume change upon protein denaturation. Because of the strength of NMR in studying protein structure and function, NMR techniques are receiving renewed interest in pressure studies of proteins.

Two methods are available for NMR studies at high pressure; one employs a thick wall NMR sample tube inside a commercial NMR probe and the other utilizes a dedicated NMR probe with sample and detection coils enclosed within an external pressure vessel. [High Pressure NMR, National Magnetic Resonance Facility, Univ. of Wisconsin- Madison, US, 1999] http://www.nmrfam.wisc.edu/Research/pressure.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.

Google = about 12,500 June 7, 2004

Industrial Macromolecular Crystallography Association IMCA:  http://www.imca.aps.anl.gov/

Related terms: beamline, synchrotrons

infrared spectromicroscopy: Microscopy

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 (NMR) detection coupled with liquid chromatography (LC) offers great promise in combining the ability to separate complex mixtures into individual components with one of the most structurally rich detection schemes available. [Bert Wang, Introduction to LC- NMR Technology, Wang NMR, Inc. 2002   http://www.wangnmr.com/LCNMR_technology.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: Recent developments in synchrotron radiation sources have revolutionized protein crystallography, opening the door to high- throughput protein- structure determination. These intense tunable X-ray sources have allowed the development of the Multi-wavelength Anomalous Dispersion (MAD) technique for solving the phasing problem. MAD enables the collection of data in mere minutes compared with the many hours required when conventional X-ray sources were used. Protein crystallography,  DOE Genomes to Life, US http://www.doegenomestolife.org/technology/crystallography.html

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

Google = about 12,800 June 7, 2004

Narrower term: hrMAS

macromolecular crystallography: The study of the structures of large biological molecules contained in crystals. "Large" in this context means that the molecules consist of 400 atoms and up. Biological macromolecules rarely exist as crystals in their natural state, so part of the science consists of coercing the molecules (usually proteins, but occasionally DNA and RNA molecules) to form crystals. Typical crystals of macromolecules are 10-500 microns (0.01 mm - 0.5 mm) in each dimension. IMCA- CAT: A Layman's Introduction http://www.imca.aps.anl.gov/

metabolomics: -Omes & -omics

metabonome, metabonomics: -Omes & -omics

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]  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 BioSpin] http://www.bruker-biospin.com/nmr/products/crp_micro.html

Related terms: cryogenic probes, cryoprobe.

mmCIF dictionary Macromolecular Crystallographic Information File:  http://ndbserver.rutgers.edu/mmcif/
Background and introduction http://ndbserver.rutgers.edu/mmcif/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. 

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. 

Narrower terms:  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, 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/coi/cda/home.cda?chId=5

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 based screening: Assays & screening

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, 1998]

NMR spin relaxation spectroscopy: A powerful approach for characterizing intramolecular and overall rotational motions in proteins. This review describes experimental methods for measuring laboratory frame spin relaxation rate constants by high- resolution solution- state NMR spectroscopy, together with theoretical approaches for interpreting spin relaxation data in order to quantify protein conformational dynamics on picosecond- nanosecond time scales. AG Palmer 3rd NMR probes of molecular dynamics: overview and comparison with other techniques. Annual Rev Biophys Biomol Struct.30:129- 155, 2001

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. 

neutron crystallography: A valuable technique to use when details of an enzyme mechanism or binding site for drug development are needed. Although not a high- throughput procedure, neutron crystallography can visualize the hydrogen atoms (about half the atoms in a protein structure). It can also visualize many of the more- mobile water molecules that cannot be seen, even with ultrahigh resolution synchrotron X-ray radiation. Protein crystallography,  DOE Genomes to Life, US http://www.doegenomestolife.org/technology/crystallography.html

neutron scattering: Helps to resolve how the 3-D parts of protein machines fit together and how proteins communicate in dynamic regulatory and signaling networks. While nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography provide high-resolution structural information on individual subunits of protein and protein- DNA complexes, neutron scattering provides lower-resolution information on the shapes and arrangements of these subunits in solution, thereby complementing these other tools...  Neutron scattering shows much promise for structural analyses of protein complexes, but it faces several technical limitations. Neutron scattering Technology, DOE Genomes to Life, US http://www.doegenomestolife.org/technology/neutronscattering.html

phasing techniques: Include Multiple Anonymous Dispersion MAD phasing, Multiple Isomorphous Replacement MIR Bernhard Rupp, Protein Crystallography Tutorial Site, 2005  http://ruppweb.dyndns.org/Xray/101index.html 

protein crystallography: Over the years, the laborious and painstaking process of protein crystallography has resulted in an increasingly large number of protein and nucleic acid structures. Crystallography is essential for studying the 3-D structure of these biomolecules and for revealing some of the mechanisms of their biological activity. However, the structures solved by crystallography are static: they are a snapshot image of the molecule's motion and chemical activity.

In contrast with time-averaged still images from protein crystallography, other analytical tools can provide dynamic structural information, something that could be considered a motion picture of a molecule's behavior. These tools include a variety of spectroscopic techniques such as fluorescence studies, electron paramagnetic resonance, and nuclear magnetic resonance; and scattering techniques such as quasi-elastic and dynamic light scattering, and X-ray and neutron small-angle scattering. Protein crystallography,  DOE Genomes to Life, US http://www.doegenomestolife.org/technology/crystallography.html

Is there any kind of protein crystallography that isn't x-ray crystallography?  

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. 

Google = about 35,700 June 7, 2004

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/index.html 

Quantitative ¹³C NMR Spectrometric Data- Activity Relationships Modeling QSDAR:

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. 

Related term: triple resonance NMR

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

Narrower term: chemical relaxation 

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. 

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. 

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. 

sp-NMR: An information system to support the design of selective, high affinity inhibitors of the binding of HIV Tat protein to the P/CAF Bromodomain. To facilitate data sharing and collaborations on this research project, SP-NMR offers information obtained when conducting focused NMR compound binding assays and presents an integrated view of the data to inform the rational drug- design process.  The goals of sp-NMR include to: Support investigators conducting NMR-based drug-design studies; Integrate diverse experimental results and data types produced by these studies;  Institute for Computational Biomedicine, Weill Medical College of Cornell University, 2003-2005 http://icb.med.cornell.edu/crt/Arcadia/query.xml 

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: Ultrasensitivity

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). 

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.  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] 

Narrower terms:  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

Synchrotron Radiation Circular Dichroism (SRCD) spectroscopy: Molecular Imaging

structure based NMR screening: Assays & screening

Superconducting QUantum Interference Devices SQUIDs: The most sensitive magnetic field detector ever devised ... SQUIDs have been used in NMR measurements since the 1980s, but mostly for solid samples at extremely low temperatures... SQUIDs can detect magnetic flux directly, sensing the magnetic field generated by even a slowly precessing nucleus. The resulting signal is weak but extremely sharp: the lower the magnetic field, the narrower the NMR line, yielding a signal- to- noise ratio far superior to that of high- field NMR.  [Paul Preuss "Measuring molecules with minute magnetic fields" Lawrence Berkeley Lab, US, 2002] http://www.lbl.gov/Science-Articles/Archive/MSD-microtesla-Clarke.html

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, 1993]

A large machine that accelerates electrically charged particles to nearly the speed of light and maintains them in circular 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]

Google = about 741,000 June 7, 2004

Related terms beamline: Industrial Macromolecular Crystallography Association IMCA;  Nanoscience & Miniaturization  nanoscience

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

synchrotron-based X-ray crystallography:  an area of study committed to solving detailed structures of molecules. The field has exploded in recent years, and a major threat to its continued growth is limited synchrotron resources. Synchrotrons are the enormous machines that produce powerful X-ray beams used by researchers to tease apart the three- dimensional structures of molecules.  [NIH Funds Synchrotron Beamlines to Advance Studies of Molecular Structures, NIGMS press release, Nov. 5, 2001] http://www.nigms.nih.gov/news/releases/beamline.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.

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.

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.

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.

X-ray crystallography is an experimental technique that exploits the fact that X-rays are diffracted by crystals. It is not an imaging technique.  Bernard Rupp, Crystallography 101 http://www.imca.aps.anl.gov/ 

Related terms: beamlines, protein crystallography, 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] 

x-ray crystallography: An experimental technique that exploits the fact that X-rays are diffracted by crystals. It is not an imaging technique. Bernhard Rupp, Crystallography 101  http://ruppweb.dyndns.org/Xray/101index.html  

Bibliography
Campbell, Robert L., Protein crystallography: Important points and definitions, Dept. of Biophysics and Biochemistry, Johns Hopkins Univ., US, 23 definitions and bibliography. http://biophysics.med.jhu.edu/rlc/lect/definitions.html
Clark, Jim, Understanding Chemistry, Nuclear Magnetic Resonance menu http://www.chemguide.co.uk/analysis/nmrmenu.html#top
Holton, James, Elves Manual Glossary of X-ray Terms *, Univ. of California Berkeley, US http://ucxray.berkeley.edu/~jamesh/elves/manual/basics.html
Hornak, JP, Basics of NMR: Glossary,  Rochester Institute of Technology, US 1997-1999 http://www.cis.rit.edu/htbooks/nmr/inside.htm
IUCR International Union of Crystallography, Statistical descriptors in Crystallography, Glossary of statistical terms, 1996 http://www.iucr.org/iucr-top/comm/cnom/statdes/index.html#gloss
IUCR International Union of Crystallography, Virtual Library: Crystallography http://www.ch.iucr.org/cww-top/int.w3vlc.html
IUPAC Recommendations: NMR Nomenclature: Nuclear Spin Properties and Conventions for Chemical Shifts, Robin K. Harris et. al, Physical and Biophysical Chemistry Division, Commission Molecular Structure and Spectroscopy, 2001 
http://www.iupac.org/publications/pac/2001/7311/7311x1795.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/iupac.pdf 
Joint Center for Structural Genomics, Important Definitions, 40+ terms http://www.jcsg.org/help/robohelp/Definitions/Intro_to_Definitions.htm 
Otter, Albin, AO-VNMR Glossary, Chemistry Dept. Univ. of Alberta, Canada, 2001.  http://nmr.chem.ualberta.ca/AOWWW/  About 50 terms.
Rhodes, Gale, 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.)
Rhodes, Gale, Judging the Quality of Macromolecular models Glossary of Terms from Crystallography, NMR and Homology Modeling, Chemistry Dept. Univ. of Southern Maine, US, 2000 http://www.usm.maine.edu/~rhodes/ModQual/index.html
Rupp, Bernhard, Crystallography 101, http://ruppweb.dyndns.org/Xray/101index.html 

Alpha glossary index

How to look for other unfamiliar  terms