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Protein Technologies glossary & taxonomy
Evolving Terminology for Emerging Technologies
Comments? Questions? Revisions?  Mary Chitty  mchitty@healthtech.com
Last revised June 28, 2012
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2D gel electrophoresis: A key technology for proteomics. Chromatography & electrophoresis glossary

antibody arrays: Microarrays & protein chips categories for studying regulation at the protein level

antibody display:  de Kruif J,, Boel E, Logtenberg T. Selection and application of human single chain Fv antibody fragments from a semi-synthetic phage antibody display library with designed CDR3 regions. J Mol Biol. 1995 Apr 21;248 (1): 97-105, April 1995 .  Google = about 17,200 Nov 13, 2006, about 34,800 Feb 14, 2011

aptamers: Technologies overview

bacteriophage: Many phage have proved useful in the study of molecular biology and as vectors for the transfer of genetic information between cells … lambda bacteriophage can also undergo a lytic cycle or can enter a lysogenic cycle, in which the page DNA is incorporated into that of the host, awaiting a signal that initiates events leading to replication of the virus and lysis of the host cell. Glick

The workhorse of phage display is the M13 bacteriophage virus. Related terms: phage, phage display bacteriophage, biopanning, phage;  Labels, signaling & detection     Proteomics directed protein evolution

biopanning: Encompasses aspects of both ‘encoded one bead, one compound’ and the reductive approaches employed in chemistry. Biopanning is generally applied to display libraries, such as phage, bacterial, ribosome , RNA or on-bead display libraries, in which proteins are physically linked to their encoding sequence. This enables large libraries to be expressed and screened en masse for their ligand- binding properties. The library is screened by several rounds of biopanning, whereby the complexes are incubated with the desired target molecule, which is typically immobilized on a solid support. Subsequent washing removes the weakly binding proteins while retaining the desired proteins, which are then eluted for the next round of biopanning. Successively smaller numbers of displayed proteins are screened until ‘active’ proteins are isolated. The identity of the active protein borne on the display vehicle is established by sequencing the linked encoding sequence (DNA or RNA) of the carrier vehicle (phage, bacteria, ribosome or bead). Marcus D. Hughes, Zhan-Ren Zhang, Andrew J. Sutherland, Albert F. Santos and Anna V. Hine, Discovery of active proteins directly from combinatorial randomized protein libraries without display, purification or sequencing: identification of novel zinc finger proteins, Nucleic Acids Research 2005 33(3) http://nar.oupjournals.org/cgi/content/full/33/3/e32   Also referred to as panning.

carbohydrate chips, carbohydrate microarrays: Microarrays & protein chips categories

cDNA phage display:  Display cloning: functional identification of natural product receptors using cDNA-phage display.  Sche PP, McKenzie KM, White JD, Austin DJ. Chem Biol. 1999 Oct;6(10):707- 716  Google = about 537 Nov 13, 2006

co-immunoprecipitation  Used to determine protein- protein interactions.  An antibody is used to precipitate a protein along with bound proteins. John Yates, “Mass spectrometry and the Age of the Proteome”  Journal Mass Spectrometry 33: 16, 1998

combinatorial biology: Involves genetic manipulation of bacteria and fungi that produce complex natural products. This technology includes construction of large libraries of recombinant microbes capable of generating novel organic molecules and engineering secondary metabolite biosynthetic pathways to modify valuable biologically active microbial metabolites. [ASB [Am Soc. Biomechanics] Newsletter, June 1998]   http://asb-biomech.org/newsletter/V11N1/guest.html    Wikipedia http://en.wikipedia.org/wiki/Combinatorial_biology   Related term: phage display

co-precipitation: Method to identify interacting proteins by using antibodies to bind to the protein if immunoprecipitated under non- denaturing using conditions … (allow any other proteins bound to the protein known to be involved in a process) to precipitate rather than be washed away.

depletion:  Method of sample preparation which removes high abundance proteins (not of interest) from the sample. Related term:  low- abundance proteins.

directed protein evolution: Proteomics Related term: phage display 

DNA shuffling: Genomic technologies Can be used to evolve proteins.

domain shuffling: Protein structure  Google = about 862 Aug. 20, 2003; about 2,030 Nov. 29, 2004; about 25,400 Nov 13, 2006

fluorescent proteins: Using fluorescence is turning into one of the premier technologies for drug discovery. To tap the full potential of these new and exciting opportunities, many challenges still need to be addressed: How to increase the stability of cell lines expressing fluorescent proteins; how to increase drug screening by using better disease models utilizing FP’s in whole organisms; how to develop better tools to enhance the high-throughput applications; and how to improve effectiveness while lowering costs.  Related terms: Labels Signaling & Detection  

Fluorescence Recovery After Photobleaching FRAP, Fluorescence Resonance Energy Transfer FRET: Labels Signaling & Detection

fusion proteins: A fusion protein is the product of joining two genes or two proteins / peptides together. Fusion proteins can happen naturally or it can be created artificially in a laboratory for research purposes. This is achieved through the creation of a fusion gene which is done through the removal of the stop codon from a DNA sequence of the first protein and then attaching the DNA sequence of the second protein in frame. The resulting DNA sequence will then be expressed by a cell as a single protein. International Society for Complexity, Information and Design http://www.iscid.org/encyclopedia/Fusion_Protein     Wikipedia http://en.wikipedia.org/wiki/Fusion_protein

fusion proteins, recombinant: Proteins that are the result of genetic engineering.  A regulatory part or promoter of one or more genes is combined with a structural gene. The fusion protein is formed after transcription and translation of the fused gene. This type of fusion protein is used in the study of gene regulation or structure- activity relationships. They might also be used clinically as targeted toxins (immunotoxins). MeSH, 1987  Related term: cell fusion

gene shuffling: Genomic technologies  Can be used to evolve proteins.

glycoarrays, glycoprotein microarrays: Microarrays & protein chips categories

interaction proteomics:   Protein- protein interactions lie at the heart of most cellular processes … A complete understanding of cellular function depends on a full characterization of the complex network of cellular protein- protein associations …. Alternative proteomics technologies are being developed to complement the two- hybrid system. These methods reveal direct protein- protein interactions by using protein affinity chromatography. Protein affinity chromatography, as developed by Greenblatt, Alberts, and colleagues, has the disadvantage of requiring purified proteins as reagents, but it is superior to the two- hybrid approach because it generates fewer false positives and is more amenable to high- throughput screening. [Aled Edwards et al. “Proteomics: new tools for a new era” Modern Drug Discovery 3 (7): 35- 44 Sept. 2000]  http://pubs.acs.org/journals/mdd/toc/0900toc.html  Related terms:  protein- DNA interactions, protein- protein interactions, protein- RNA interactions, reverse two- hybrid, yeast one- hybrid, yeast- two hybrid; yeast three- hybrid,  co- precipitation, co- immunoprecipitation; Maps genetic & genomic  cell mapping, maps- protein, peptide mapping, protein interaction mapping, protein linkage maps; Omes & omics glossary interactome  Related/equivalent term?: interaction proteomics

interactome, interactomics: Omes & omics glossary

intrabodies: Recent advances in antibody engineering have now allowed the genes encoding antibodies to be manipulated so that the antigen binding domain can be expressed intracellularly. The specific and high- affinity binding properties of antibodies, combined with their ability to be stably expressed in precise intracellular locations inside mammalian cells, has provided a powerful new family of molecules for gene therapy applications. These intracellular antibodies are termed 'intrabodies'. [Wayne A. Marasco, "Intrabodies: turning the humoral immune system outside in for intracellular immunization" Gene Therapy 4 (1): 11- 15, Jan. 1997] 

Isotope Coded Infinity Tag ICAT:  These tags provide the ability to both identify and quantify a broad range of proteins in a high- throughput mode. Using ICAT reagents, researchers can compare the expression levels of proteins from two samples, such as from normal and diseased cells. ICAT reagents comprise a protein reactive group, an affinity tag (biotin), and an isotopically labeled linker. Related term: protein profiling

lambda phage: See under bacteriophage
molecular display: See under phage display
molecular evolution: Technologies overview

molecular motors: Protein based machines that are involved in or cause movement such as the rotary devices (flagellar motor and the F1 ATPase) or the devices whose movement is directed along cytoskeletal filaments (myosin, kinesin and dynein motor families). MeSH, 1999  Google = about 8,110 Aug. 8, 2002; about 25,400 June 23, 2004, 143,000 Dec 26, 2007
Wikipedia http://en.wikipedia.org/wiki/Molecular_motors

peptide aptamers: Engineered protein molecules selected from combinatorial libraries, [used] to dissect the function of specific genes and alleles, and to trace genetic pathways. Roger Brent "Peptide aptamers" Molecular Sciences Institute, 1999  Broader term: aptamers 

Peptide Mass Fingerprinting PMF: A means of protein identification, using mass spectrometry

peptide sequencing: How is this different from protein sequencing (except that peptides are shorter than proteins)?

phage: A virus for which the natural host is a bacterial cell. DOE

Used as a vector for cloning segments of DNA. Schlindwein  Related terms: bacteriophage, phage display. 

phage display: Phage and Yeast Display April 30 - May 1, 2012 • Boston, MA Program | Register | Download Brochure

Use of genetically engineered phage to present peptides as segments of their native surface proteins. Peptide libraries may be produced by populations of phage with different gene sequences. IUPAC Combinatorial Chemistry  Broader term: display technologies  Related terms:  bacteriophage, biopanning, phage;  Labels, signaling & detection; Proteomics directed protein evolution  

photoaptamers: Aptamers that incorporate a brominated deoxyuridine (BrdU) in place of the thymidine (T) normally found in DNA. A photoaptamer recognizes both the complex shape and charge distribution of its protein target and the presence of specific amino acid residues at specific sites. Related term: spiegelmer; Broader term: aptamers

prefractionation: Sample preparation method, capable of  being automated.

protein arrays: Microarrays & protein chips glossary  Google = about  2,050 Sept. 18, 2002; about 10,200 July 14, 2004; about 194,000 June 11, 2007

protein capture reagents:  The Common Fund’s Protein Capture Reagents program is developing new resources and tools to understand the critical role the multitude of cellular proteins play in normal development and health as well as in disease. These resources will support a wide-range of research and clinical applications that will enable the isolation and tracking of proteins of interest and permit their use as diagnostic biomarkers of disease onset and progression. NIH Common Fund http://commonfund.nih.gov/proteincapture/ 
protein delivery: Drug discovery & development

protein detection: New fluorescent stains (such as Sypro) have improved both the dynamic range of protein detection and protein quantification in 2D gels. "Current State of  Proteomic Technology"  CHI's Genome Link 3.1, 2001 http://www.chidb.com/newsarticles/issue3_1.ASP

protein-DNA interactions: Can be detected by DNA footprinting, gel shift analysis, yeast one hybrid assays or Southwestern blots. John A Wagner "The logic of molecular approaches to biological problems" Cornell University Medical College  http://www-users.med.cornell.edu/~jawagne/logic_&_experimental_desig.html 

Can also be analyzed by genetic analysis and X-ray crystallography.  John Little Biochemistry Fall 2000, University of Arizona  Related terms: Proteomics categories  interaction proteomics

protein engineering: A technique used to produce proteins with altered or novel amino acid sequences. The methods used are: 1. Transcription and translation systems from synthesized lengths of DNA or RNA with novel sequences. 2. Chemical modification of  'normal' proteins. 3. Solid-  state polypeptide synthesis to form proteins.  IUPAC Compendium

Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes. MeSH 2003

Procedures by which nonrandom single- site changes are introduced into structural genes (site- specific mutagenesis) in order to produce mutant genes which can be coupled to promoters that direct the synthesis of a specifically altered protein, which is then analyzed for structural and functional properties and then compared with the predicted and sought- after properties. The design of the protein may be assisted by computer graphic technology and other advanced molecular modeling techniques.  MeSH, 1989
PEGS: the essential protein engineering summit  May 9-13, 2011 • Boston, MA  Program | Register | Download Brochure  

The Protein Engineering Department combines biological, structural, chemical, and combinatorial approaches to explore protein functions and molecular interactions. … Specific achievements include: Improving existing proteins and enzymes to make them more effective — with higher affinity, longer lasting effects and/or greater selectivity  Determining three-dimensional structures of proteins and protein complexes  Finding new molecules with biological activity and exploring their potential as therapeutic agents or drug targets  Inventing new protein/peptide technologies  Applying chemical approaches to problems in drug discovery and biology. Genentech, Protein Engineering Science of Biotechnology http://www.gene.com/gene/research/biotechnology/proteinengineering.html 

Wikipedia http://en.wikipedia.org/wiki/Protein_engineering 

protein expression profiling: Expression genes & proteins

protein inhibition: An alternative approach to [gene expression] downregulation, but in this case, the protein, not the gene, is the target. As with downregulation of gene expression, protein inhibition is a powerful target validation tool. The major approach to protein inhibition is based on phage libraries, which are used to select antibodies against targets of interest. 

protein knockouts: Our proteomics efforts are focused largely on developing new techniques to probe protein- protein interactions and to construct devices that allow one to monitor the levels and post- translational modification states of hundreds or even thousands of proteins simultaneously. A third major goal is to develop “protein knockout” methods that would allow researchers to rapidly develop reagents to block one or more functions of a newly discovered protein to facilitate studies of its role in cellular metabolism. [Thomas J. Kodadek, Internal Medicine and Molecular Biology, Univ. of Texas Southwestern Graduate Biomedical School, 2001]   http://www2.utsouthwestern.edu/gradschool/webrib/kodadek.htm  

Google = about  24 Sept. 18, 2002; about 63, July 14, 2004 about 89 Nov. 29, 2004; about 179 Nov. 10, 2006; about 253 June 18, 2007, about 2,030 March 4 2011

protein localization:  There is an ever- increasing number of genes that have been sequenced but are of completely unknown function. The ability to determine the location of such gene products within the cell, either by the use of antibodies or by the production of chimeras with green fluorescent protein, is a vital step towards understanding what they do. This is one major reason why fluorescence microscopy is enjoying a revival. Protein Localization by Fluorescence Microscopy: A Practical Approach Edited by VICTORIA J. ALLAN, Oxford University Press, 2000 http://www.oup-usa.org/isbn/0199637415.html

Protein expression analysis can indicate what proteins are expressed, but it is also important to know where proteins are expressed, and where they go over time (as with secreted proteins). Accordingly, there is an increasing shift away from general protein expression analysis and toward mapping proteins’ distribution, relative abundance, tissue specificity, and movement. By tracking these parameters (in healthy versus diseased tissue and in control versus treated tissue), researchers can gain a greater understanding of these proteins’ functions and determine which are likely to be the best drug targets. Protein localization studies can be classified as being done at a tissue or subcellular level. "Protein Localization Studies provide key insights into protein function" CHI's GenomeLink 15.2 http://www.chidb.com/newsarticles/issue15_2.asp  Narrower terms: subcellular localization, tissue specific localization; Related terms Cell biology:  subcellular fractionation; Gene definitions: gene localization; Omes & omics localizome

protein microarrays: Microarrays & protein chips glossary  Google = about  1,410 Sept. 18, 2002; about 4,380 Aug. 18, 2003' about 11,000 July 14, 2004; about 198,000 Nov 10, 2006

protein profiling: Expression glossary  Google = about 1,290 Sept. 18, 2002; about 2,820 Aug. 18, 2003, about 6,700 July 14, 2004; about 192,000 Nov 10, 2006

protein pulldowns: High- throughput analyses afforded by mass spectroscopy require sample preparation processes that can keep pace. Standardization and automation of protein “pulldowns”, and related reagents are being developed. The processes are designed to provide a straightforward material flow in high- throughput format for the pulldown of protein complexes from the Rhodopseudomonas palustris and Shewanella oneidensis genomes. Existing techniques are well developed; however, some processes in clone library, antibody, and protein complex production have never been automated and few established protocols are available.  P.R. Hoyt,  Automation of Protein Complex Analyses in Rhodopseudomonas palustris and Shewanella oneidensis, DOE, Genomes to Life, 2003 http://doegenomestolife.org/pubs/2003abstracts/html/GTL.htm

protein purification: John Wagner's Logic of Molecular Approaches to Biological Problems (Cornell Univ. Graduate School of Medical Science, US ) has a section on the value of protein purification. http://www-users.med.cornell.edu/~jawagne/proteins_%26_purification.html

protein shuffling: We also constructed a computational method to determine the locations of crossovers that lead to functional hybrid proteins during in vitro recombination. Borrowing a concept from the schema theory of genetic algorithms, our approach assumes that crossovers resulting in functional proteins are those that least disrupt structural integrity. ... This method can be used to predict sites for protein shuffling and to screen sequence databases to determine optimal sets of starting sequences for in vitro evolution by recombination. Stephen L. Mayo, Computational Protein Design, Cal Tech, Howard Hughes Medical Institute http://www.hhmi.org/research/investigators/mayo.html Google = about 16 Sept. 8, 2003; about 30 Nov. 29, 2004; about 115 Nov. 10, 2006

proteolysis: Wikipedia http://en.wikipedia.org/wiki/Proteolysis  Research and diagnostic applications

proteolytic processing: Related terms proteolysis Broader term post- translational modification

proteome arrays, proteome chips: Microarrays & protein chips glossary Google = about 76 Sept. 18, 2002; about 120 Aug. 18, 2003, about 208 July 14, 2004; about 1,620 Nov 10, 2006

proteomics technologies: Major types include protein separation, ultrafiltration, 1D and 2D gel electrophoresis, liquid chromatography, capillary electrophoresis, mass spectrometry, protein informatics, protein arrays, protein quantification, protein localization, and protein- protein interactions. 

The application of proteomics technologies to clinical research and public health in general is an immediate goal of proteomics. A distantly related goal is the eventual application of proteomics to environmental, agricultural and veterinary research, research areas that are far less developed than clinical applications. Defining the Mandate of Proteomics in the Post- Genomics Era, Board on International Scientific Organizations, National Academy of Sciences, 2002 http://www.nap.edu/books/NI000479/html/R1.html

For a field so laden with razzmatazz methods, it is striking that the number one need in proteomics may be new technology. There are simply not enough assays that are sufficiently streamlined to allow the automation necessary to perform them on a genome's worth of proteins. Those currently available barely scratch the surface of the thousands of specialized analyses biologists use every day on their favorite proteins. What we need are experimental strategies that could be termed cell biological genomics, biophysical genomics, physiological genomics, and so on, to provide clues to function. In addition, a protein contains so many types of information that each of its properties needs to be assayed on a proteome- wide scale, ideally in a quantitative manner. Stanley Fields "Proteomics in Genomeland" Science 291: 1221-1224 Feb. 16, 2001

proteomimetics - small molecule

proteoinformatics: http://dir.niehs.nih.gov/proteomics/informtx.htm  Google = about 11 Sept. 18, 2002; about 48 Aug, 18, 2003; about 244 July 14, 2004; about 200 Nov 10, 2006 

quantitative proteomics: At the Institute for Systems Biology (ISB), quantitative proteomics technologies have been developed to comprehensively identify and quantify proteins in two or more complex samples. The techniques are based on the use of stable isotopes to differentially label proteins or peptides, and mass spectrometry to compare the relative abundance of the proteins in different samples. Once proteins are differentially labeled with stable isotopes, they can be distinguished during mass spectrometry by a characteristic mass shift. In addition, the relative abundance of isotopically-labeled peptide pairs can be determined by comparing the ion signal intensities of the peptides. Institute for Systems Biology, 2010 http://www.systemsbiology.org/technology/data_generation/Quantitative_Proteomics
Wikipedia http://en.wikipedia.org/wiki/Quantitative_proteomics

recombinant proteins:  Proteins prepared by recombinant DNA technology.  MeSH, 1986  Related term: genetic recombination  

self-assembling biomolecular materials: Examples of self- assembly include protein folding, the formation of liposomes, and the alignment of liquid crystals. While this type of equilibrium self- assembly is the central focus of this report, it is important to emphasize that much biological assembly is also driven by energy sources such as adenosine triphosphate (ATP), which power biomotors  Biomolecular self- assembling materials, National Academy of Sciences 1996  http://www.nas.edu/bpa/reports/bmm/bmm.html#PBMM  Broader term: self-assembly

shotgun proteomics: Instrumentation aside, algorithms for matching mass spectra to proteins are at the heart of shotgun proteomics. How do these algorithms work, what can we expect of them and why is it so difficult to find protein modifications? Shotgun proteomics is a remarkably powerful technology for identifying proteins, whether individually or in samples as complex as cell lysates.  How do shotgun proteomics algorithms identify proteins? Edward M. Marcotte Nature Biotechnology 25, 755 - 757 (2007) doi:10.1038/nbt0707-755 http://www.nature.com/nbt/journal/v25/n7/full/nbt0707-755.html
Wikipedia http://en.wikipedia.org/wiki/Shotgun_proteomics

subcellular localization:  A variety of approaches—including tagging and fluorescence technologies, cellular isolation methods, gels, and mass spectrometry—are being used in these studies, which aim to track the location and/or movement of proteins or protein complexes in subcellular compartments.  "Protein Localization Studies provide key insights into protein function" CHI's GenomeLink 15.2 http://www.chidb.com/newsarticles/issue15_2.asp 

subcellular proteomics: See under subproteomics  Google = about 903 Nov 5, 2005

subcellular tissue-specific localization: A major methodology is an immunohistochemistry approach that uses antibodies (typically visualized via an enzyme- linked antibody assay) that specifically bind to proteins of interest. This method allows one not only to assess levels of a protein but also to localize the protein within cells in a tissue sample.  "Protein Localization Studies provide key insights into protein function" CHI's GenomeLink http://www.chidb.com/newsarticles/issue15_2.asp 

subproteomics: Advances in the field of proteomics have made it possible to search for differences in protein expression between AM [alveolar macrophages] and their precursor monocytes. Proteome features of each cell type provide new clues into understanding mononuclear phagocyte biology. In-depth analyses using subproteomics and subcellular proteomics offer additional information by providing greater protein resolution and detection sensitivity. HM Wu, M Jin, CB Marsh, Toward functional proteomics of alveolar macrophages, Am J Physiol Lung Cell Mol Physiol. 288(4): L585- 595, April 2005 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15757951&query_hl=42

Subproteomics, utilising up to 40 two-dimensional gels per sample will become a powerful tool for near- to- total proteome analysis in the postgenome era. Furthermore, this new approach can direct biological focus towards molecules of specific interest within complex cells and thus simplify efforts in discovery- based proteome research. SJ Cordwell, AS Nouwens, NM Verrills, DJ Basseal, BJ Walsh, Subproteomics based upon protein cellular location and relative solubilities in conjunction with composite two- dimensional electrophoresis gels, Electrophoresis, 21(6): 1094- 103, April 2000 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10786883&query_hl=42   Google = about 265 Nov 5, 2005

subtractive proteomics:  Molecular Imaging, Jan Schnitzer, Nov. 2004  Google = about 130 June 29, 2004

targeted proteomics: Biochemical approaches to proteomics, particularly using mass spectrometry  Google - about 365 Sept. 10, 2003

translation:  Sequences, DNA & beyond  Another approach to downregulating gene expression See also Genetic Manipulation & Disruption  RNAi; Pharmaceutical biology antisense; RNA  ribozymes. 

yeast display: See Biologics: antibody libraries

Bibliography
NFCR Center for Therapeutic Antibody Engineering Glossary, National Foundation for Cancer Research, Dana Farber Cancer Institute  http://research4.dfci.harvard.edu/nfcr-ctae/research/tech_glossary.php 
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IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.