1.
Jmol
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Jmol is computer software for molecular modelling chemical structures in 3-dimensions. Jmol returns a 3D representation of a molecule that may be used as a teaching tool and it is written in the programming language Java, so it can run on the operating systems Windows, macOS, Linux, and Unix, if Java is installed. It is free and open-source software released under a GNU Lesser General Public License version 2.0, a standalone application and a software development kit exist that can be integrated into other Java applications, such as Bioclipse and Taverna. A popular feature is an applet that can be integrated into web pages to display molecules in a variety of ways, for example, molecules can be displayed as ball-and-stick models, space-filling models, ribbon diagrams, etc. Jmol supports a range of chemical file formats, including Protein Data Bank, Crystallographic Information File, MDL Molfile. There is also a JavaScript-only version, JSmol, that can be used on computers with no Java, the Jmol applet, among other abilities, offers an alternative to the Chime plug-in, which is no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS9. Jmol requires Java installation and operates on a variety of platforms. For example, Jmol is fully functional in Mozilla Firefox, Internet Explorer, Opera, Google Chrome, fast and Scriptable Molecular Graphics in Web Browsers without Java3D
2.
ChEMBL
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ChEMBL or ChEMBLdb is a manually curated chemical database of bioactive molecules with drug-like properties. It is maintained by the European Bioinformatics Institute, of the European Molecular Biology Laboratory, based at the Wellcome Trust Genome Campus, Hinxton, the database, originally known as StARlite, was developed by a biotechnology company called Inpharmatica Ltd. later acquired by Galapagos NV. The data was acquired for EMBL in 2008 with an award from The Wellcome Trust, resulting in the creation of the ChEMBL chemogenomics group at EMBL-EBI, the ChEMBL database contains compound bioactivity data against drug targets. Bioactivity is reported in Ki, Kd, IC50, and EC50, data can be filtered and analyzed to develop compound screening libraries for lead identification during drug discovery. ChEMBL version 2 was launched in January 2010, including 2.4 million bioassay measurements covering 622,824 compounds and this was obtained from curating over 34,000 publications across twelve medicinal chemistry journals. ChEMBLs coverage of available bioactivity data has grown to become the most comprehensive ever seen in a public database, in October 2010 ChEMBL version 8 was launched, with over 2.97 million bioassay measurements covering 636,269 compounds. ChEMBL_10 saw the addition of the PubChem confirmatory assays, in order to integrate data that is comparable to the type, ChEMBLdb can be accessed via a web interface or downloaded by File Transfer Protocol. It is formatted in a manner amenable to computerized data mining, ChEMBL is also integrated into other large-scale chemistry resources, including PubChem and the ChemSpider system of the Royal Society of Chemistry. In addition to the database, the ChEMBL group have developed tools and these include Kinase SARfari, an integrated chemogenomics workbench focussed on kinases. The system incorporates and links sequence, structure, compounds and screening data, the primary purpose of ChEMBL-NTD is to provide a freely accessible and permanent archive and distribution centre for deposited data. July 2012 saw the release of a new data service, sponsored by the Medicines for Malaria Venture. The data in this service includes compounds from the Malaria Box screening set, myChEMBL, the ChEMBL virtual machine, was released in October 2013 to allow users to access a complete and free, easy-to-install cheminformatics infrastructure. In December 2013, the operations of the SureChem patent informatics database were transferred to EMBL-EBI, in a portmanteau, SureChem was renamed SureChEMBL. 2014 saw the introduction of the new resource ADME SARfari - a tool for predicting and comparing cross-species ADME targets
3.
ChemSpider
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ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The search can be used to widen or restrict already found results, structure searching on mobile devices can be done using free apps for iOS and for the Android. The ChemSpider database has been used in combination with text mining as the basis of document markup. The result is a system between chemistry documents and information look-up via ChemSpider into over 150 data sources. ChemSpider was acquired by the Royal Society of Chemistry in May,2009, prior to the acquisition by RSC, ChemSpider was controlled by a private corporation, ChemZoo Inc. The system was first launched in March 2007 in a release form. ChemSpider has expanded the generic support of a database to include support of the Wikipedia chemical structure collection via their WiChempedia implementation. A number of services are available online. SyntheticPages is an interactive database of synthetic chemistry procedures operated by the Royal Society of Chemistry. Users submit synthetic procedures which they have conducted themselves for publication on the site and these procedures may be original works, but they are more often based on literature reactions. Citations to the published procedure are made where appropriate. They are checked by an editor before posting. The pages do not undergo formal peer-review like a journal article. The comments are moderated by scientific editors. The intention is to collect practical experience of how to conduct useful chemical synthesis in the lab, while experimental methods published in an ordinary academic journal are listed formally and concisely, the procedures in ChemSpider SyntheticPages are given with more practical detail. Comments by submitters are included as well, other publications with comparable amounts of detail include Organic Syntheses and Inorganic Syntheses
4.
European Chemicals Agency
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ECHA is the driving force among regulatory authorities in implementing the EUs chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and it is located in Helsinki, Finland. The Agency, headed by Executive Director Geert Dancet, started working on 1 June 2007, the REACH Regulation requires companies to provide information on the hazards, risks and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most commonly used substances have been registered, the information is technical but gives detail on the impact of each chemical on people and the environment. This also gives European consumers the right to ask whether the goods they buy contain dangerous substances. The Classification, Labelling and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU. This worldwide system makes it easier for workers and consumers to know the effects of chemicals, companies need to notify ECHA of the classification and labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100000 substances, the information is freely available on their website. Consumers can check chemicals in the products they use, Biocidal products include, for example, insect repellents and disinfectants used in hospitals. The Biocidal Products Regulation ensures that there is information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation, the law on Prior Informed Consent sets guidelines for the export and import of hazardous chemicals. Through this mechanism, countries due to hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have effects on human health and the environment are identified as Substances of Very High Concern 1. These are mainly substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment, other substances considered as SVHCs include, for example, endocrine disrupting chemicals. Companies manufacturing or importing articles containing these substances in a concentration above 0 and they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy, once a substance has been officially identified in the EU as being of very high concern, it will be added to a list. This list is available on ECHA’s website and shows consumers and industry which chemicals are identified as SVHCs, Substances placed on the Candidate List can then move to another list
5.
IUPHAR/BPS
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The IUPHAR/BPS Guide to PHARMACOLOGY is an open-access website, acting as a portal to information on the biological targets of licensed drugs and other small molecules. The Guide to PHARMACOLOGY is developed as a joint venture between the International Union of Basic and Clinical Pharmacology and the British Pharmacological Society and this replaces and expands upon the original 2009 IUPHAR Database. The information featured includes pharmacological data, target and gene nomenclature, overviews and commentaries on each target family are included, with links to key references. The Guide to PHARMACOLOGY was initially made available online in December 2011 with additional material released in July 2012 and its network of over 700 specialist advisors contribute expertise and data. The current PI and Grant holder of the GtoPdb project is Prof. Jamie A. Davies, the development and release of the first version of the GtoPdb in 2012 was described in an editorial published in the British Journal of Pharmacology entitled Guide to Pharmacology. org- an update. The IUPHAR-DB is no longer being developed and all the contained within this site is now available through the Guide to PHARMACOLOGY. A complete list of all the approved drugs included on the website is available via the ligand list. The Guide to PHARMACOLOGY is being expanded to include information on targets and ligands. Search features on the website include quick and advanced search options, other features include Hot topic news items and a recent receptor-ligand pairing list. A hard copy summary of the database is published as The Concise Guide to Pharmacology 2015/2016 as a series of papers as a bi-annual supplement to the British Journal of Pharmacology. The Guide to PHARMACOLOGY includes links to other relevant resources via target, many of these resources maintain reciprocal links with the relevant Guide to PHARMACOLOGY pages. As of November 2015 the Wellcome Trust is supporting a new project to develop the Guide to Immumopharmacology, the latter continues to be supported by the British Pharmacological Society
6.
PubChem
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PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information, a component of the National Library of Medicine, PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be downloaded via FTP. PubChem contains substance descriptions and small molecules with fewer than 1000 atoms and 1000 bonds, more than 80 database vendors contribute to the growing PubChem database. PubChem consists of three dynamically growing primary databases, as of 28 January 2016, Compounds,82.6 million entries, contains pure and characterized chemical compounds. Substances,198 million entries, contains also mixtures, extracts, complexes, bioAssay, bioactivity results from 1.1 million high-throughput screening programs with several million values. PubChem contains its own online molecule editor with SMILES/SMARTS and InChI support that allows the import and export of all common chemical file formats to search for structures and fragments. In the text search form the database fields can be searched by adding the name in square brackets to the search term. A numeric range is represented by two separated by a colon. The search terms and field names are case-insensitive, parentheses and the logical operators AND, OR, and NOT can be used. AND is assumed if no operator is used, example,0,5000,50,10 -5,5 PubChem was released in 2004. The American Chemical Society has raised concerns about the publicly supported PubChem database and they have a strong interest in the issue since the Chemical Abstracts Service generates a large percentage of the societys revenue. To advocate their position against the PubChem database, ACS has actively lobbied the US Congress, soon after PubChems creation, the American Chemical Society lobbied U. S. Congress to restrict the operation of PubChem, which they asserted competes with their Chemical Abstracts Service
7.
International Chemical Identifier
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Initially developed by IUPAC and NIST from 2000 to 2005, the format and algorithms are non-proprietary. The continuing development of the standard has supported since 2010 by the not-for-profit InChI Trust. The current version is 1.04 and was released in September 2011, prior to 1.04, the software was freely available under the open source LGPL license, but it now uses a custom license called IUPAC-InChI Trust License. Not all layers have to be provided, for instance, the layer can be omitted if that type of information is not relevant to the particular application. InChIs can thus be seen as akin to a general and extremely formalized version of IUPAC names and they can express more information than the simpler SMILES notation and differ in that every structure has a unique InChI string, which is important in database applications. Information about the 3-dimensional coordinates of atoms is not represented in InChI, the InChI algorithm converts input structural information into a unique InChI identifier in a three-step process, normalization, canonicalization, and serialization. The InChIKey, sometimes referred to as a hashed InChI, is a fixed length condensed digital representation of the InChI that is not human-understandable. The InChIKey specification was released in September 2007 in order to facilitate web searches for chemical compounds and it should be noted that, unlike the InChI, the InChIKey is not unique, though collisions can be calculated to be very rare, they happen. In January 2009 the final 1.02 version of the InChI software was released and this provided a means to generate so called standard InChI, which does not allow for user selectable options in dealing with the stereochemistry and tautomeric layers of the InChI string. The standard InChIKey is then the hashed version of the standard InChI string, the standard InChI will simplify comparison of InChI strings and keys generated by different groups, and subsequently accessed via diverse sources such as databases and web resources. Every InChI starts with the string InChI= followed by the version number and this is followed by the letter S for standard InChIs. The remaining information is structured as a sequence of layers and sub-layers, the layers and sub-layers are separated by the delimiter / and start with a characteristic prefix letter. The six layers with important sublayers are, Main layer Chemical formula and this is the only sublayer that must occur in every InChI. The atoms in the formula are numbered in sequence, this sublayer describes which atoms are connected by bonds to which other ones. Describes how many hydrogen atoms are connected to each of the other atoms, the condensed,27 character standard InChIKey is a hashed version of the full standard InChI, designed to allow for easy web searches of chemical compounds. Most chemical structures on the Web up to 2007 have been represented as GIF files, the full InChI turned out to be too lengthy for easy searching, and therefore the InChIKey was developed. With all databases currently having below 50 million structures, such duplication appears unlikely at present, a recent study more extensively studies the collision rate finding that the experimental collision rate is in agreement with the theoretical expectations. Example, Morphine has the structure shown on the right, as the InChI cannot be reconstructed from the InChIKey, an InChIKey always needs to be linked to the original InChI to get back to the original structure
8.
Simplified molecular-input line-entry system
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The simplified molecular-input line-entry system is a specification in form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules, the original SMILES specification was initiated in the 1980s. It has since modified and extended. In 2007, a standard called OpenSMILES was developed in the open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. The Environmental Protection Agency funded the project to develop SMILES. It has since modified and extended by others, most notably by Daylight Chemical Information Systems. In 2007, a standard called OpenSMILES was developed by the Blue Obelisk open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, in July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is generally considered to have the advantage of being slightly more human-readable than InChI, the term SMILES refers to a line notation for encoding molecular structures and specific instances should strictly be called SMILES strings. However, the term SMILES is also used to refer to both a single SMILES string and a number of SMILES strings, the exact meaning is usually apparent from the context. The terms canonical and isomeric can lead to confusion when applied to SMILES. The terms describe different attributes of SMILES strings and are not mutually exclusive, typically, a number of equally valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol, algorithms have been developed to generate the same SMILES string for a given molecule, of the many possible strings, these algorithms choose only one of them. This SMILES is unique for each structure, although dependent on the algorithm used to generate it. These algorithms first convert the SMILES to a representation of the molecular structure. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database, there is currently no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, and these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES
9.
Chemical formula
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These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, the simplest types of chemical formulas are called empirical formulas, which use letters and numbers indicating the numerical proportions of atoms of each type. Molecular formulas indicate the numbers of each type of atom in a molecule. For example, the formula for glucose is CH2O, while its molecular formula is C6H12O6. This is possible if the relevant bonding is easy to show in one dimension, an example is the condensed molecular/chemical formula for ethanol, which is CH3-CH2-OH or CH3CH2OH. For reasons of structural complexity, there is no condensed chemical formula that specifies glucose, chemical formulas may be used in chemical equations to describe chemical reactions and other chemical transformations, such as the dissolving of ionic compounds into solution. A chemical formula identifies each constituent element by its chemical symbol, in empirical formulas, these proportions begin with a key element and then assign numbers of atoms of the other elements in the compound, as ratios to the key element. For molecular compounds, these numbers can all be expressed as whole numbers. For example, the formula of ethanol may be written C2H6O because the molecules of ethanol all contain two carbon atoms, six hydrogen atoms, and one oxygen atom. Some types of compounds, however, cannot be written with entirely whole-number empirical formulas. An example is boron carbide, whose formula of CBn is a variable non-whole number ratio with n ranging from over 4 to more than 6.5. When the chemical compound of the consists of simple molecules. These types of formulas are known as molecular formulas and condensed formulas. A molecular formula enumerates the number of atoms to reflect those in the molecule, so that the formula for glucose is C6H12O6 rather than the glucose empirical formula. However, except for very simple substances, molecular chemical formulas lack needed structural information, for simple molecules, a condensed formula is a type of chemical formula that may fully imply a correct structural formula. For example, ethanol may be represented by the chemical formula CH3CH2OH
10.
Aqueous solution
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An aqueous solution is a solution in which the solvent is water. It is usually shown in chemical equations by appending to the relevant chemical formula, for example, a solution of table salt, or sodium chloride, in water would be represented as Na+ + Cl−. The word aqueous means pertaining to, related to, similar to, as water is an excellent solvent and is also naturally abundant, it is a ubiquitous solvent in chemistry. Substances that are hydrophobic often do not dissolve well in water, an example of a hydrophilic substance is sodium chloride. Acids and bases are aqueous solutions, as part of their Arrhenius definitions, the ability of a substance to dissolve in water is determined by whether the substance can match or exceed the strong attractive forces that water molecules generate between themselves. If the substance lacks the ability to dissolve in water the molecules form a precipitate, reactions in aqueous solutions are usually metathesis reactions. Metathesis reactions are another term for double-displacement, that is, when a cation displaces to form a bond with the other anion. The cation bonded with the latter anion will dissociate and bond with the other anion, aqueous solutions that conduct electric current efficiently contain strong electrolytes, while ones that conduct poorly are considered to have weak electrolytes. Those strong electrolytes are substances that are ionized in water. Nonelectrolytes are substances that dissolve in water yet maintain their molecular integrity, examples include sugar, urea, glycerol, and methylsulfonylmethane. When writing the equations of reactions, it is essential to determine the precipitate. To determine the precipitate, one must consult a chart of solubility, soluble compounds are aqueous, while insoluble compounds are the precipitate. Remember that there may not always be a precipitate, when performing calculations regarding the reacting of one or more aqueous solutions, in general one must know the concentration, or molarity, of the aqueous solutions. Solution concentration is given in terms of the form of the prior to it dissolving. Metal ions in aqueous solution Solubility Dissociation Acid-base reaction theories Properties of water Zumdahl S.1997, 4th ed. Boston, Houghton Mifflin Company
11.
Refractive index
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In optics, the refractive index or index of refraction n of a material is a dimensionless number that describes how light propagates through that medium. It is defined as n = c v, where c is the speed of light in vacuum, for example, the refractive index of water is 1.333, meaning that light travels 1.333 times faster in a vacuum than it does in water. The refractive index determines how light is bent, or refracted. The refractive indices also determine the amount of light that is reflected when reaching the interface, as well as the angle for total internal reflection. This implies that vacuum has a index of 1. The refractive index varies with the wavelength of light and this is called dispersion and causes the splitting of white light into its constituent colors in prisms and rainbows, and chromatic aberration in lenses. Light propagation in absorbing materials can be described using a refractive index. The imaginary part then handles the attenuation, while the real part accounts for refraction, the concept of refractive index is widely used within the full electromagnetic spectrum, from X-rays to radio waves. It can also be used with wave phenomena such as sound, in this case the speed of sound is used instead of that of light and a reference medium other than vacuum must be chosen. Thomas Young was presumably the person who first used, and invented, at the same time he changed this value of refractive power into a single number, instead of the traditional ratio of two numbers. The ratio had the disadvantage of different appearances, newton, who called it the proportion of the sines of incidence and refraction, wrote it as a ratio of two numbers, like 529 to 396. Hauksbee, who called it the ratio of refraction, wrote it as a ratio with a fixed numerator, hutton wrote it as a ratio with a fixed denominator, like 1.3358 to 1. Young did not use a symbol for the index of refraction, in the next years, others started using different symbols, n, m, and µ. For visible light most transparent media have refractive indices between 1 and 2, a few examples are given in the adjacent table. These values are measured at the yellow doublet D-line of sodium, with a wavelength of 589 nanometers, gases at atmospheric pressure have refractive indices close to 1 because of their low density. Almost all solids and liquids have refractive indices above 1.3, aerogel is a very low density solid that can be produced with refractive index in the range from 1.002 to 1.265. Moissanite lies at the end of the range with a refractive index as high as 2.65. Most plastics have refractive indices in the range from 1.3 to 1.7, for infrared light refractive indices can be considerably higher
12.
Relative permittivity
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The relative permittivity of a material is its permittivity expressed as a ratio relative to the permittivity of vacuum. Permittivity is a property that affects the Coulomb force between two point charges in the material. Relative permittivity is the factor by which the field between the charges is decreased relative to vacuum. Likewise, relative permittivity is the ratio of the capacitance of a capacitor using that material as a dielectric, relative permittivity is also commonly known as dielectric constant, a term deprecated in physics and engineering as well as in chemistry. Relative permittivity is typically denoted as εr and is defined as ε r = ε ε0, where ε is the complex frequency-dependent absolute permittivity of the material, and ε0 is the vacuum permittivity. Relative permittivity is a number that is in general complex-valued, its real and imaginary parts are denoted as. The relative permittivity of a medium is related to its electric susceptibility, χe, in anisotropic media the relative permittivity is a second rank tensor. The relative permittivity of a material for a frequency of zero is known as its relative permittivity. The historical term for the relative permittivity is dielectric constant and it is still commonly used, but has been deprecated by standards organizations, because of its ambiguity, as some older authors used it for the absolute permittivity ε. The permittivity may be quoted either as a property or as a frequency-dependent variant. It has also used to refer to only the real component εr of the complex-valued relative permittivity. In the causal theory of waves, permittivity is a complex quantity, the imaginary part corresponds to a phase shift of the polarization P relative to E and leads to the attenuation of electromagnetic waves passing through the medium. By definition, the relative permittivity of vacuum is equal to 1. The relative static permittivity, εr, can be measured for static electric fields as follows, first the capacitance of a test capacitor, then, using the same capacitor and distance between its plates, the capacitance Cx with a dielectric between the plates is measured. The relative dielectric constant can be calculated as ε r = C x C0. For time-variant electromagnetic fields, this quantity becomes frequency-dependent, an indirect technique to calculate εr is conversion of radio frequency S-parameter measurement results. A description of frequently used S-parameter conversions for determination of the frequency-dependent εr of dielectrics can be found in this bibliographic source, alternatively, resonance based effects may be employed at fixed frequencies. The relative permittivity is a piece of information when designing capacitors
13.
Infrared spectroscopy
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Infrared spectroscopy involves the interaction of infrared radiation with matter. It covers a range of techniques, mostly based on absorption spectroscopy, as with all spectroscopic techniques, it can be used to identify and study chemicals. Sample may be solid, liquid, or gas, the method or technique of infrared spectroscopy is conducted with an instrument called an infrared spectrometer to produce an infrared spectrum. An IR spectrum is essentially a graph of infrared light absorbance on the vertical axis vs. frequency or wavelength on the horizontal axis, typical units of frequency used in IR spectra are reciprocal centimeters, with the symbol cm−1. Units of IR wavelength are commonly given in micrometers, symbol μm, a common laboratory instrument that uses this technique is a Fourier transform infrared spectrometer. Two-dimensional IR is also possible as discussed below, the infrared portion of the electromagnetic spectrum is usually divided into three regions, the near-, mid- and far- infrared, named for their relation to the visible spectrum. The higher-energy near-IR, approximately 14000–4000 cm−1 can excite overtone or harmonic vibrations, the mid-infrared, approximately 4000–400 cm−1 may be used to study the fundamental vibrations and associated rotational-vibrational structure. The far-infrared, approximately 400–10 cm−1, lying adjacent to the region, has low energy. The names and classifications of these subregions are conventions, and are loosely based on the relative molecular or electromagnetic properties. Infrared spectroscopy exploits the fact that molecules absorb frequencies that are characteristic of their structure and these absorptions occur at resonant frequencies, i. e. the frequency of the absorbed radiation matches the vibrational frequency. The energies are affected by the shape of the potential energy surfaces, the masses of the atoms. In particular, in the Born–Oppenheimer and harmonic approximations, i. e, the resonant frequencies are also related to the strength of the bond and the mass of the atoms at either end of it. Thus, the frequency of the vibrations are associated with a normal mode of motion. In order for a mode in a sample to be IR active. A permanent dipole is not necessary, as the rule requires only a change in dipole moment, a molecule can vibrate in many ways, and each way is called a vibrational mode. For molecules with N number of atoms, linear molecules have 3N –5 degrees of vibrational modes, as an example H2O, a non-linear molecule, will have 3 ×3 –6 =3 degrees of vibrational freedom, or modes. Simple diatomic molecules have only one bond and only one vibrational band, if the molecule is symmetrical, e. g. N2, the band is not observed in the IR spectrum, but only in the Raman spectrum. Asymmetrical diatomic molecules, e. g. CO, absorb in the IR spectrum, more complex molecules have many bonds, and their vibrational spectra are correspondingly more complex, i. e. big molecules have many peaks in their IR spectra
14.
Nuclear magnetic resonance spectroscopy
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Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is a research technique that exploits the magnetic properties of certain atomic nuclei. This type of spectroscopy determines the physical and chemical properties of atoms or the molecules in which they are contained and it relies on the phenomenon of nuclear magnetic resonance and can provide detailed information about the structure, dynamics, reaction state, and chemical environment of molecules. Suitable samples range from small compounds analyzed with 1-dimensional proton or carbon-13 NMR spectroscopy to large proteins or nucleic acids using 3 or 4-dimensional techniques. The impact of NMR spectroscopy on the sciences has been substantial because of the range of information, NMR spectra are unique, well-resolved, analytically tractable and often highly predictable for small molecules. Thus, in organic chemistry practice, NMR analysis is used to confirm the identity of a substance, different functional groups are obviously distinguishable, and identical functional groups with differing neighboring substituents still give distinguishable signals. NMR has largely replaced traditional wet chemistry tests such as reagents or typical chromatography for identification. A disadvantage is that a large amount, 2–50 mg, of a purified substance is required. Preferably, the sample should be dissolved in a solvent, because NMR analysis of solids requires a dedicated MAS machine, the timescale of NMR is relatively long, and thus it is not suitable for observing fast phenomena, producing only an averaged spectrum. NMR spectrometers are relatively expensive, universities usually have them, modern NMR spectrometers have a very strong, large and expensive liquid helium-cooled superconducting magnet, because resolution directly depends on magnetic field strength. There are even benchtop NMR spectrometers, the Purcell group at Harvard University and the Bloch group at Stanford University independently developed NMR spectroscopy in the late 1940s and early 1950s. Edward Mills Purcell and Felix Bloch shared the 1952 Nobel Prize in Physics for their discoveries, when placed in a magnetic field, NMR active nuclei absorb electromagnetic radiation at a frequency characteristic of the isotope. The resonant frequency, energy of the absorption, and the intensity of the signal are proportional to the strength of the magnetic field, for example, in a 21 Tesla magnetic field, protons resonate at 900 MHz. It is common to refer to a 21 T magnet as a 900 MHz magnet, spinning the sample is necessary to average out diffusional motion. Whereas, measurements of diffusion constants are done the sample stationary and spinning off, the vast majority of nuclei in a solution would belong to the solvent, and most regular solvents are hydrocarbons and would contain NMR-reactive protons. The most used deuterated solvent is deuterochloroform, although deuterium oxide and deuterated DMSO are used for hydrophilic analytes, the chemical shifts are slightly different in different solvents, depending on electronic solvation effects. NMR spectra are often calibrated against the known solvent residual proton peak instead of added tetramethylsilane, to detect the very small frequency shifts due to nuclear magnetic resonance, the applied magnetic field must be constant throughout the sample volume. High resolution NMR spectrometers use shims to adjust the homogeneity of the field to parts per billion in a volume of a few cubic centimeters. In order to detect and compensate for inhomogeneity and drift in the magnetic field, in modern NMR spectrometers shimming is adjusted automatically, though in some cases the operator has to optimize the shim parameters manually to obtain the best possible resolution
15.
Mass spectrometry
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Mass spectrometry is an analytical technique that ionizes chemical species and sorts the ions based on their mass-to-charge ratio. In simpler terms, a mass spectrum measures the masses within a sample, mass spectrometry is used in many different fields and is applied to pure samples as well as complex mixtures. A mass spectrum is a plot of the ion signal as a function of the mass-to-charge ratio, in a typical MS procedure, a sample, which may be solid, liquid, or gas, is ionized, for example by bombarding it with electrons. This may cause some of the molecules to break into charged fragments. The ions are detected by a capable of detecting charged particles. Results are displayed as spectra of the abundance of detected ions as a function of the mass-to-charge ratio. The atoms or molecules in the sample can be identified by correlating known masses to the masses or through a characteristic fragmentation pattern. Goldstein called these positively charged anode rays Kanalstrahlen, the translation of this term into English is canal rays. Wien found that the charge-to-mass ratio depended on the nature of the gas in the discharge tube, thomson later improved on the work of Wien by reducing the pressure to create the mass spectrograph. The word spectrograph had become part of the international scientific vocabulary by 1884, a mass spectroscope is similar to a mass spectrograph except that the beam of ions is directed onto a phosphor screen. A mass spectroscope configuration was used in early instruments when it was desired that the effects of adjustments be quickly observed, once the instrument was properly adjusted, a photographic plate was inserted and exposed. The term mass spectroscope continued to be used though the direct illumination of a phosphor screen was replaced by indirect measurements with an oscilloscope. The use of the mass spectroscopy is now discouraged due to the possibility of confusion with light spectroscopy. Mass spectrometry is often abbreviated as mass-spec or simply as MS, modern techniques of mass spectrometry were devised by Arthur Jeffrey Dempster and F. W. Aston in 1918 and 1919 respectively. Sector mass spectrometers known as calutrons were used for separating the isotopes of uranium developed by Ernest O. Lawrence during the Manhattan Project, calutron mass spectrometers were used for uranium enrichment at the Oak Ridge, Tennessee Y-12 plant established during World War II. In 1989, half of the Nobel Prize in Physics was awarded to Hans Dehmelt, a mass spectrometer consists of three components, an ion source, a mass analyzer, and a detector. The ionizer converts a portion of the sample into ions, there is a wide variety of ionization techniques, depending on the phase of the sample and the efficiency of various ionization mechanisms for the unknown species. An extraction system removes ions from the sample, which are then targeted through the mass analyzer, the differences in masses of the fragments allows the mass analyzer to sort the ions by their mass-to-charge ratio
16.
Genetic code
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The genetic code is the set of rules by which information encoded within genetic material is translated into proteins by living cells. Translation is accomplished by the ribosome, which links amino acids in an order specified by mRNA, using transfer RNA molecules to carry amino acids, the genetic code is highly similar among all organisms and can be expressed in a simple table with 64 entries. The code defines how sequences of nucleotide triplets, called codons, with some exceptions, a three-nucleotide codon in a nucleic acid sequence specifies a single amino acid. The vast majority of genes are encoded with a single scheme and that scheme is often referred to as the canonical or standard genetic code, or simply the genetic code, though variant codes exist. While the genetic code determines a proteins amino acid sequence, other genomic regions determine when, efforts to understand how proteins are encoded began after DNAs structure was discovered in 1953. George Gamow postulated that sets of three bases must be employed to encode the 20 standard amino acids used by living cells to build proteins, the Crick, Brenner et al. experiment first demonstrated that codons consist of three DNA bases. Marshall Nirenberg and Heinrich J. Matthaei were the first to reveal the nature of a codon in 1961 and they used a cell-free system to translate a poly-uracil RNA sequence and discovered that the polypeptide that they had synthesized consisted of only the amino acid phenylalanine. They thereby deduced that the codon UUU specified the amino acid phenylalanine, therefore, the codon AAA specified the amino acid lysine, and the codon CCC specified the amino acid proline. Using various copolymers most of the remaining codons were then determined, subsequent work by Har Gobind Khorana identified the rest of the genetic code. Shortly thereafter, Robert W. Holley determined the structure of transfer RNA and this work was based upon Ochoas earlier studies, yielding the latter the Nobel Prize in Physiology or Medicine in 1959 for work on the enzymology of RNA synthesis. Extending this work, Nirenberg and Philip Leder revealed the triplet nature. In these experiments, various combinations of mRNA were passed through a filter that contained ribosomes, unique triplets promoted the binding of specific tRNAs to the ribosome. Leder and Nirenberg were able to determine the sequences of 54 out of 64 codons in their experiments, Khorana, Holley and Nirenberg received the 1968 Nobel for their work. The three stop codons were named by discoverers Richard Epstein and Charles Steinberg, amber was named after their friend Harris Bernstein, whose last name means amber in German. The other two stop codons were named ochre and opal in order to keep the color names theme, H. Murakami and M. Sisido extended some codons to have four and five bases. Steven A. Benner constructed a functional 65th codon, in 2016 the first stable semisynthetic organism was created. It was a bacterium with two synthetic bases, in 2017 a mouse engineered with an extended genetic code that can produce proteins with unnatural amino acids was reported. A codon is defined by the initial nucleotide from which starts and sets the frame for a run of successive triplets
17.
Amino acid
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Amino acids are organic compounds containing amine and carboxyl functional groups, along with a side chain specific to each amino acid. The key elements of an acid are carbon, hydrogen, oxygen. About 500 amino acids are known and can be classified in many ways, in the form of proteins, amino acids comprise the second-largest component of human muscles, cells and other tissues. Outside proteins, amino acids perform critical roles in such as neurotransmitter transport. In biochemistry, amino acids having both the amine and the acid groups attached to the first carbon atom have particular importance. They are known as 2-, alpha-, or α-amino acids and they include the 22 proteinogenic amino acids, which combine into peptide chains to form the building-blocks of a vast array of proteins. These are all L-stereoisomers, although a few D-amino acids occur in bacterial envelopes, as a neuromodulator, twenty of the proteinogenic amino acids are encoded directly by triplet codons in the genetic code and are known as standard amino acids. The other two are selenocysteine, and pyrrolysine, pyrrolysine and selenocysteine are encoded via variant codons, for example, selenocysteine is encoded by stop codon and SECIS element. N-formylmethionine is generally considered as a form of methionine rather than as a separate proteinogenic amino acid, codon–tRNA combinations not found in nature can also be used to expand the genetic code and create novel proteins known as alloproteins incorporating non-proteinogenic amino acids. Many important proteinogenic and non-proteinogenic amino acids also play critical roles within the body. Nine proteinogenic amino acids are called essential for humans because they cannot be created from other compounds by the human body, others may be conditionally essential for certain ages or medical conditions. Essential amino acids may also differ between species, because of their biological significance, amino acids are important in nutrition and are commonly used in nutritional supplements, fertilizers, and food technology. Industrial uses include the production of drugs, biodegradable plastics, the first few amino acids were discovered in the early 19th century. In 1806, French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet isolated a compound in asparagus that was subsequently named asparagine, cystine was discovered in 1810, although its monomer, cysteine, remained undiscovered until 1884. Glycine and leucine were discovered in 1820, usage of the term amino acid in the English language is from 1898. Proteins were found to yield amino acids after enzymatic digestion or acid hydrolysis, in the structure shown at the top of the page, R represents a side chain specific to each amino acid. The carbon atom next to the group is called the α–carbon. Amino acids containing an amino group bonded directly to the alpha carbon are referred to as amino acids
18.
Protein
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Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, a linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide, short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides, or sometimes oligopeptides. The individual amino acid residues are bonded together by peptide bonds, the sequence of amino acid residues in a protein is defined by the sequence of a gene, which is encoded in the genetic code. In general, the code specifies 20 standard amino acids, however. Sometimes proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors, proteins can also work together to achieve a particular function, and they often associate to form stable protein complexes. Once formed, proteins only exist for a period of time and are then degraded and recycled by the cells machinery through the process of protein turnover. A proteins lifespan is measured in terms of its half-life and covers a wide range and they can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal and or misfolded proteins are degraded more rapidly due to being targeted for destruction or due to being unstable. Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms, many proteins are enzymes that catalyse biochemical reactions and are vital to metabolism. Proteins also have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, other proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized, digestion breaks the proteins down for use in the metabolism. Methods commonly used to study structure and function include immunohistochemistry, site-directed mutagenesis, X-ray crystallography, nuclear magnetic resonance. Most proteins consist of linear polymers built from series of up to 20 different L-α-amino acids, all proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group, a carboxyl group, and a variable side chain are bonded. Only proline differs from this structure as it contains an unusual ring to the N-end amine group. The amino acids in a chain are linked by peptide bonds. Once linked in the chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen. The peptide bond has two forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are roughly coplanar
19.
Essential amino acid
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An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized de novo by the organism, and thus must be supplied in its diet. The nine amino acids humans cannot synthesize are phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine and these six are arginine, cysteine, glycine, glutamine, proline, and tyrosine. Five amino acids are dispensable in humans, meaning they can be synthesized in the body and these five are alanine, aspartic acid, asparagine, glutamic acid and serine. Pyrrolysine, sometimes considered the 22nd amino acid, is not used by humans, eukaryotes can synthesize some of the amino acids from other substrates. Consequently, only a subset of the amino acids used in protein synthesis are essential nutrients, estimating the daily requirement for the indispensable amino acids has proven to be difficult, these numbers have undergone considerable revision over the last 20 years. The following table lists the WHO recommended daily amounts currently in use for essential amino acids in adult humans, food sources are identified based on the USDA National Nutrient Database Release. The recommended daily intakes for children aged three years and older is 10% to 20% higher than adult levels and those for infants can be as much as 150% higher in the first year of life, cysteine, tyrosine, and arginine are always required by infants and growing children. Various attempts have been made to express the quality or value of various kinds of protein, measures include the biological value, net protein utilization, protein efficiency ratio, protein digestibility-corrected amino acid score and complete proteins concept. Thus, various feedstuffs may be fed in combination to increase net protein utilization, eating various plant foods in combination can provide a protein of higher biological value. Certain native combinations of foods, such as corn and beans, soybeans and rice, or red beans and rice, for example, while 100 g of raw broccoli only provides 28 kcal and 3 g of protein, it has over 100 mg of protein per kcal. An egg contains five times as many calories but only four times as much protein, however, a carrot has only 23 mg protein per kcal or twice the minimum recommendation, a banana meets the minimum, and an apple is below recommendation. It is recommended that adult humans obtain 10–35% of their calories as protein, the US FDA daily reference value of 50 g protein per 2000 kcal is 25 mg/kcal per day. This led William Cumming Rose to the discovery of the amino acid threonine. Roses later work showed that eight amino acids are essential for human beings. Longer term studies established histidine as also essential for adult humans, the distinction between essential and non-essential amino acids is somewhat unclear, as some amino acids can be produced from others. The sulfur-containing amino acids, methionine and homocysteine, can be converted into each other but neither can be synthesized de novo in humans, likewise, cysteine can be made from homocysteine but cannot be synthesized on its own. So, for convenience, sulfur-containing amino acids are considered a single pool of nutritionally equivalent amino acids as are the aromatic amino acid pair. Likewise arginine, ornithine, and citrulline, which are interconvertible by the cycle, are considered a single group
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Histidine
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Histidine is an α-amino acid that is used in the biosynthesis of proteins. It contains a group, a carboxylic acid group. Initially thought essential only for infants, longer-term studies have shown it is essential for adults also, Histidine was first isolated by German physician Albrecht Kossel and Sven Hedin in 1896. It is also a precursor to histamine, an inflammatory agent in immune responses. The conjugate acid of the side chain in histidine has a pKa of approximately 6.0. This means that, at physiologically relevant pH values, relatively small shifts in pH will change its average charge, below a pH of 6, the imidazole ring is mostly protonated as described by the Henderson–Hasselbalch equation. When protonated, the ring bears two NH bonds and has a positive charge. The positive charge is distributed between both nitrogens and can be represented with two equally important resonance structures. As the pH increases past approximately 6, one of the protons is lost, the remaining proton of the now-neutral imidazole ring can reside on either nitrogen, giving rise to what are known as the N1-H or N3-H tautomers. When both imidazole ring nitrogens are protonated, their 15N chemical shifts are similar, NMR shows that the chemical shift of N1-H drops slightly, whereas the chemical shift of N3-H drops considerably. This indicates that the N1-H tautomer is preferred, it is presumed due to hydrogen bonding to the neighboring ammonium, as the pH rises above 9, the chemical shifts of N1 and N3 become approximately 185 and 170 ppm. An entirely deprotonated form of the ring, the imidazolate ion, would be formed only above a pH of 14. This change in chemical shifts can be explained by the presumably decreased hydrogen bonding of an amine over an ammonium ion, and this should act to decrease the N1-H tautomer preference. The imidazole ring of histidine is aromatic at all pH values and it contains six pi electrons, four from two double bonds and two from a nitrogen lone pair. It can form pi stacking interactions, but is complicated by the positive charge and it does not absorb at 280 nm in either state, but does in the lower UV range more than some amino acids. The imidazole sidechain of histidine is a coordinating ligand in metalloproteins and is a part of catalytic sites in certain enzymes. It has the ability to switch between protonated and unprotonated states, which allows histidine to participate in acid-base catalysis, in catalytic triads, the basic nitrogen of histidine is used to abstract a proton from serine, threonine, or cysteine to activate it as a nucleophile. In a histidine proton shuttle, histidine is used to quickly shuttle protons and it can do this by abstracting a proton with its basic nitrogen to make a positively charged intermediate and then use another molecule, a buffer, to extract the proton from its acidic nitrogen
21.
Epsilon
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Epsilon is the fifth letter of the Greek alphabet, corresponding phonetically to a mid front unrounded vowel /e/. In the system of Greek numerals it has the value five and it was derived from the Phoenician letter He. Letters that arose from epsilon include the Roman E, Ë and Ɛ, in essence, the uppercase form of epsilon looks identical to Latin E. The lowercase version has two variants, both inherited from medieval Greek handwriting. One, the most common in typography and inherited from medieval minuscule. The other, also known as lunate or uncial epsilon and inherited from earlier uncial writing, while in normal typography these are just alternative font variants, they may have different meanings as mathematical symbols. Computer systems therefore offer distinct encodings for them, in Unicode, the character U+0一3F5 Greek lunate epsilon symbol is provided specifically for the lunate form. In TeX, \epsilon denotes the lunate form, while \varepsilon denotes the reversed-3 form, there is also a Latin epsilon or open e, which looks similar to the Greek lowercase epsilon. It is encoded in Unicode as U+025B and U+0190 and is used as an IPA phonetic symbol, the lunate or uncial epsilon has also provided inspiration for the euro sign. The lunate epsilon is not to be confused with the set membership symbol, in addition, mathematicians have read the symbol ∈ as element of, as in 1 is an element of the natural numbers for 1 ∈ N, for example. As late as 1960, ϵ itself was used for set membership, Only gradually did a fully separate stylized symbol take the place of epsilon. In a related context, Peano also introduced the use of a backwards epsilon, ∍, for the phrase such that, the letter Ε was taken over from the Phoenician letter He when Greeks first adopted alphabetic writing. In archaic Greek writing, its shape is often identical to that of the Phoenician letter. Archaic writing often preserves the Phoenician form with a stem extending slightly below the lowest horizontal bar. In the classical era, through the influence of cursive writing styles. Besides its classical Greek sound value, the short /e/ phoneme, for instance, in early Attic before c.500 B. C. it was used also both for the long, open /ɛː/, and for the long close /eː/. In the former role, it was replaced in the classic Greek alphabet by Eta. Some dialects used yet other ways of distinguishing between various e-like sounds, in Corinth, the normal function of Ε to denote /e/ and /ɛː/ was taken by a glyph resembling a pointed B, while Ε was used only for long close /eː/
22.
Catalysis
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Catalysis is the increase in the rate of a chemical reaction due to the participation of an additional substance called a catalyst. In most cases, reactions occur faster with a catalyst because they require less activation energy, furthermore, since they are not consumed in the catalyzed reaction, catalysts can continue to act repeatedly. Often only tiny amounts are required in principle, in the presence of a catalyst, less free energy is required to reach the transition state, but the total free energy from reactants to products does not change. A catalyst may participate in multiple chemical transformations, the effect of a catalyst may vary due to the presence of other substances known as inhibitors or poisons or promoters. Catalyzed reactions have an activation energy than the corresponding uncatalyzed reaction, resulting in a higher reaction rate at the same temperature. However, the mechanics of catalysis is complex. Usually, the catalyst participates in this slowest step, and rates are limited by amount of catalyst, in heterogeneous catalysis, the diffusion of reagents to the surface and diffusion of products from the surface can be rate determining. A nanomaterial-based catalyst is an example of a heterogeneous catalyst, analogous events associated with substrate binding and product dissociation apply to homogeneous catalysts. Although catalysts are not consumed by the reaction itself, they may be inhibited, deactivated, in heterogeneous catalysis, typical secondary processes include coking where the catalyst becomes covered by polymeric side products. Additionally, heterogeneous catalysts can dissolve into the solution in a system or sublimate in a solid–gas system. The production of most industrially important chemicals involves catalysis, similarly, most biochemically significant processes are catalysed. Research into catalysis is a field in applied science and involves many areas of chemistry, notably organometallic chemistry. Catalysis is relevant to aspects of environmental science, e. g. the catalytic converter in automobiles. Many transition metals and transition metal complexes are used in catalysis as well, Catalysts called enzymes are important in biology. A catalyst works by providing a reaction pathway to the reaction product. The rate of the reaction is increased as this route has a lower activation energy than the reaction route not mediated by the catalyst. The disproportionation of hydrogen peroxide creates water and oxygen, as shown below,2 H2O2 →2 H2O + O2 This reaction is preferable in the sense that the reaction products are more stable than the starting material, though the uncatalysed reaction is slow. In fact, the decomposition of hydrogen peroxide is so slow that hydrogen peroxide solutions are commercially available and this reaction is strongly affected by catalysts such as manganese dioxide, or the enzyme peroxidase in organisms
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Post-translational modification
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Post-translational modification refers to the covalent and generally enzymatic modification of proteins during or after protein biosynthesis. Proteins are synthesized by ribosomes translating mRNA into polypeptide chains, which may then undergo PTM to form the protein product. PTMs are important components in cell signaling, post-translational modifications can occur on the amino acid side chains or at the proteins C- or N- termini. They can extend the chemical repertoire of the 20 standard amino acids by modifying an existing functional group or introducing a new one such as phosphate, phosphorylation is a very common mechanism for regulating the activity of enzymes and is the most common post-translational modification. Attachment of lipid molecules, known as lipidation, often targets a protein or part of an attached to the cell membrane. Other forms of post-translational modification consist of cleaving peptide bonds, as in processing a propeptide to a form or removing the initiator methionine residue. The formation of bonds from cysteine residues may also be referred to as a post-translational modification. Some types of modification are consequences of oxidative stress. Carbonylation is one example that targets the modified protein for degradation, specific amino acid modifications can be used as biomarkers indicating oxidative damage. In addition, although the amide of asparagine is a weak nucleophile, rarer modifications can occur at oxidized methionines and at some methylenes in side chains. Post-translational modification of proteins can be detected by a variety of techniques, including mass spectrometry, Eastern blotting. O-acylation, N-acylation, S-acylation acetylation, the addition of an acetyl group, formylation alkylation, the addition of an alkyl group, e. g. methyl, ethyl methylation the addition of a methyl group, usually at lysine or arginine residues. Formed by oxidative dissociation of a C-terminal Gly residue, amide bond formation amino acid addition arginylation, a tRNA-mediation addition polyglutamylation, covalent linkage of glutamic acid residues to the N-terminus of tubulin and some other proteins. Distinct from glycation, which is regarded as an attachment of sugars. Glycation, the addition of a molecule to a protein without the controlling action of an enzyme. Carbamylation the addition of Isocyanic acid to a proteins N-terminus or the side-chain of Lys. carbonylation the addition of carbon monoxide to other organic/inorganic compounds, biotinylation, covalent attachment of a biotin moiety using a biotinylation reagent, typically for the purpose of labeling a protein. Carbamylation, the addition of Isocyanic acid to a proteins N-terminus or the side-chain of Lys or Cys residues, oxidation, addition of one or more Oxygen atoms to a susceptible side-chain, principally of Met, Trp, His or Cys residues. Formation of disulfide bonds between Cys residues, pegylation, covalent attachment of polyethylene glycol using a pegylation reagent, typically to the N-terminus or the side-chains of Lys residues
24.
Methyllysine
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In proteins, the amino acid residue lysine can be methylated once, twice or thrice on its terminal sidechain ammonium group. The binding is affected because the radius of the positive charge is increased. Moreover, the groups are themselves hydrophobic, and alter the structure of water in their vicinity. It is thought that the methylation of lysine on histone tails does not directly affect their binding to DNA, rather, such methyl marks recruit other proteins that modulate chromatin structure. In Protein Data Bank files, methylated lysines are indicated by the MLY or MLZ acronyms
25.
Calmodulin
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Calmodulin is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is a target of the secondary messenger Ca2+. Once bound to Ca2+, Calmodulin acts as part of a signal transduction pathway by modifying its interactions with various target proteins such as kinases or phosphatases. Calmodulin is a small, highly conserved protein that is 148 amino acids long, the protein has two approximately symmetrical globular domains each containing a pair of EF-hand motifs separated by a flexible linker region for a total of four Ca2+ binding sites. Each EF-hand motif allows calmodulin to sense intracellular calcium levels by binding one Ca2+ ion. Calcium ion binding regions are found in the positions in the sequence of amino acids, 21-32, 57-68, 94-105 and 130-141. These regions are located between two alpha helices in the EF-hand motifs, the first two regions are on one side of the region the other two are on the other side. Calmodulin binds such a variety of target proteins, making it especially important for it to have flexibility. Another important characteristic of calmodulin that allows it to bind a large variety of proteins is the generic shape of the non-polar grooves in the binding sites. Since the non-polar grooves are generic, they dont require the target proteins to have any specific sequence of amino acids allowing a variety of target proteins to be bound. Together, these two characteristics of calmodulin allow it to flexibly bind target proteins with various shapes and amino acid sequences. For example, calmodulin binds both NMDA receptors and potassium channels which differ in length by about 50 amino acid residues, calmodulins structure is very similar to the structure of Troponin C. They are both members of the EFh superfamily, Troponin C, like Calmodulin, has two globular domains that are connected by a linker region. However, Troponin C and Calmodulin differ in the length of the linker region and these remarkably similar structures are an example of how the EF hand motif is highly conserved in calcium binding proteins. Though they have similar structures, their functions are very different, Troponin C has a very specific function ultimately causing a contraction in skeletal muscles. Calmodulin, evolved to bind a wider variety of target proteins, up to four calcium ions are bound by calmodulin via its four EF hand motifs. EF hands supply an electronegative environment for ion coordination, after calcium binding, hydrophobic methyl groups from methionine residues become exposed on the protein via conformational change. When the alpha helices are perpendicular to one another, the Calmodulin is in an open conformation giving it a higher affinity for target proteins, more specifically, this conformational change presents hydrophobic surfaces, which can in turn bind to Basic Amphiphilic Helices on the target protein
26.
Acetylation
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Acetylation describes a reaction that introduces an acetyl functional group into a chemical compound. Deacetylation is the removal of an acetyl group, Acetylation refers to the process of introducing an acetyl group into a compound, namely the substitution of an acetyl group for an active hydrogen atom. A reaction involving the replacement of the atom of a hydroxyl group with an acetyl group yields a specific ester. Acetic anhydride is used as an acetylating agent reacting with free hydroxyl groups. For example, it is used in the synthesis of aspirin and heroin, Acetylation is an important modification of proteins in cell biology, and proteomics studies have identified thousands of acetylated mammalian proteins. Acetylation occurs as a co-translational and post-translational modification of proteins, for example, histones, p53, among these proteins, chromatin proteins and metabolic enzymes are highly represented, indicating that acetylation has a considerable impact on gene expression and metabolism. In bacteria, 90% of proteins involved in metabolism of Salmonella enteric are acetylated. N-terminal acetylation is one of the most common co-translational covalent modifications of proteins in eukaryotes, N-terminal acetylation plays an important role in the synthesis, stability and localization of proteins. About 85% of all proteins and 68% in yeast are acetylated at their Nα-terminus. Several proteins from prokaryotes and archaea are also modified by N-terminal acetylation, N-terminal Acetylation is catalyzed by a set of enzyme complexes, the N-terminal acetyltransferases. NATs transfer a group from acetyl-coenzyme A to the α-amino group of the first amino acid residue of the protein. Different NATs are responsible for the acetylation of nascent protein N-termini, to date, six different NATs have been found in humans - NatA, NatB, NatC, NatD, NatE and NatF. Each of these different enzyme complexes is specific for different amino acids or amino acid sequences which is shown in the following table, the Composition and Substrate specificity of NATs. NatA is composed of two subunits, the catalytic subunit Naa10 and the auxiliary subunit Naa15, NatA subunits are more complex in higher eukaryotes than in lower eukaryotes. In addition to the genes NAA10 and NAA15, the mammal-specific genes NAA11 and NAA16, make functional gene products, four possible hNatA catalytic-auxiliary dimers are formed by these four proteins. However, Naa10/Naa15 is the most abundant NatA, NatA acetylates Ser, Ala-, Gly-, Thr-, Val- and Cys N-termini after the initiator methionine is removed by methionine amino-peptidases. These amino acids are frequently expressed in the N-terminal of proteins in eukaryotes. Several different interaction partners are involved in the N-terminal acetylation by NatA, Huntingtin interacting protein K interacts with hNatA on the ribosome to affect the N-terminal acetylation of a subset of NatA substrates
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SUMO protein
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Small Ubiquitin-like Modifier proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. SUMO proteins are similar to ubiquitin, and SUMOylation is directed by an enzymatic cascade analogous to that involved in ubiquitination, in contrast to ubiquitin, SUMO is not used to tag proteins for degradation. SUMO family members often have names, the SUMO homologue in yeast. Several pseudogenes have been reported for this gene, SUMO modification of proteins has many functions. Among the most frequent and best studied are protein stability, nuclear-cytosolic transport, typically, only a small fraction of a given protein is SUMOylated and this modification is rapidly reversed by the action of deSUMOylating enzymes. SUMOylation of target proteins has been shown to cause a number of different outcomes including altered localization, the SUMO-1 modification of RanGAP1 leads to its trafficking from cytosol to nuclear pore complex. The SUMO modification of hNinein leads to its movement from the centrosome to the nucleus, in many cases, SUMO modification of transcriptional regulators correlates with inhibition of transcription. One can refer to the GeneRIFs of the SUMO proteins, e. g. human SUMO-1, there are 4 confirmed SUMO isoforms in humans, SUMO-1, SUMO-2, SUMO-3 and SUMO-4. SUMO-2/3 show a degree of similarity to each other and are distinct from SUMO-1. SUMO-4 shows similarity to SUMO-2/3 but differs in having a Proline instead of Glutamine at position 90, as a result, SUMO-4 isnt processed and conjugated under normal conditions, but is used for modification of proteins under stress-conditions like starvation. One of the major SUMO conjugation products associated with mitotic chromosomes arose from SUMO-2/3 conjugation of topoisomerase II, SUMO-2/3 modifications seem to be involved specifically in the stress response. SUMO-1 and SUMO-2/3 can form mixed chains, however, because SUMO-1 does not contain the internal SUMO consensus sites found in SUMO-2/3, serine 2 of SUMO-1 is phosphorylated, raising the concept of a modified modifier. SUMO proteins are small, most are around 100 amino acids in length and 12 kDa in mass, the exact length and mass varies between SUMO family members and depends on which organism the protein comes from. Although SUMO has very little sequence identity with ubiquitin at the acid level. The structure of human SUMO1 is depicted on the right and it shows SUMO1 as a globular protein with both ends of the amino acid chain sticking out of the proteins centre. The spherical core consists of a helix and a beta sheet. The diagrams shown are based on an NMR analysis of the protein in solution. Most SUMO-modified proteins contain the tetrapeptide consensus motif Ψ-K-x-D/E where Ψ is a residue, K is the lysine conjugated to SUMO, x is any amino acid
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Ubiquitin
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Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. It was discovered in 1975 in Israel by Gideon Goldstein and further characterized throughout the 1970s and 1980s, there are four genes in the human genome that produce ubiquitin, UBB, UBC, UBA52 and RPS27A. The addition of ubiquitin to a protein is called ubiquitination or ubiquitylation. The protein modifications can be either a single protein or a chain of ubiquitin. The ubiquitination bonds are formed with one of the seven lysine residues as well as the very N-terminal methionine from the ubiquitin molecule. These linking residues are represented by a K or M and a number, first, a ubiquitin molecule is bonded by its C-terminus to a specific lysine residue on the target protein. This process repeats several times, leading to the addition of several ubiquitins, the discovery that ubiquitin chains target proteins to the proteasome, which degrades and recycles proteins, was honored with the Nobel Prize in chemistry in 2004. Ubiquitin was first identified in 1975 as an 8.5 kDa protein of unknown function expressed in all eukaryotic cells, the ubiquitination system was initially characterised as an ATP-dependent proteolytic system present in cellular extracts. Multiple APF-1 molecules were linked to a substrate molecule by an isopeptide linkage. Soon after APF-1-protein conjugation was characterised, APF-1 was identified as ubiquitin, the carboxyl group of the C-terminal glycine residue of ubiquitin was identified as the moiety conjugated to substrate lysine residues. Ubiquitin is a protein that exists in all eukaryotic cells. It performs its functions through conjugation to a large range of target proteins. A variety of different modifications can occur, the ubiquitin protein itself consists of 76 amino acids and has a molecular mass of about 8.5 kDa. Key features include its C-terminal tail and the 7 lysine residues and it is highly conserved among eukaryotic species, Human and yeast ubiquitin share 96% sequence identity. Ubiquitin is encoded in mammals by 4 different genes, UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. The UBB and UBC genes code for polyubiquitin precursor proteins, no ubiquitin and ubiquitination machinery are known to exist in prokaryotes. However, ubiquitin is believed to have descended from prokaryotic proteins similar to ThiS or MoaD and these prokaryotic proteins, despite having little sequence identity, share the same protein fold. These proteins also share sulfur chemistry with ubiquitin, a similar system exists for ThiS, with its E1-like enzyme ThiF
29.
Collagen
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Collagen /ˈkɒlədʒᵻn/ is the main structural protein in the extracellular space in the various connective tissues in animal bodies. As the main component of tissue, it is the most abundant protein in mammals. Depending upon the degree of mineralization, collagen tissues may be rigid, compliant, Collagen, in the form of elongated fibrils, is mostly found in fibrous tissues such as tendons, ligaments and skin. It is also abundant in corneas, cartilage, bones, blood vessels, the gut, intervertebral discs, in muscle tissue, it serves as a major component of the endomysium. Collagen constitutes one to two percent of muscle tissue, and accounts for 6% of the weight of strong, tendinous muscles, the fibroblast is the most common cell that creates collagen. Gelatin, which is used in food and industry, is collagen that has been irreversibly hydrolyzed, Collagen also has many medical uses in treating complications of the bones and skin. The name collagen comes from the Greek κόλλα, meaning glue and this refers to the compounds early use in the process of boiling the skin and sinews of horses and other animals to obtain glue. Collagen occurs in places throughout the body. Over 90% of the collagen in the body, however, is type I. So far,28 types of collagen have been identified and described, type IV, forms basal lamina, the epithelium-secreted layer of the basement membrane. Type V, cell surfaces, hair and placenta The collagenous cardiac skeleton which includes the four valve rings, is histologically, elastically and uniquely bound to cardiac muscle. The cardiac skeleton also includes the separating septa of the heart chambers – the interventricular septum, Collagen contribution to the measure of cardiac performance summarily represents a continuous torsional force opposed to the fluid mechanics of blood pressure emitted from the heart. With support from collagen, atrial fibrillation should never deteriorate to ventricular fibrillation, Collagen is layered in variable densities with cardiac muscle mass. The mass, distribution, age and density of collagen all contribute to the required to move blood back. Individual cardiac valvular leaflets are folded into shape by specialized collagen under variable pressure, gradual calcium deposition within collagen occurs as a natural function of aging. Pathology of the underpinning of the heart is understood within the category of connective tissue disease. Collagen has been used in cosmetic surgery, as a healing aid for burn patients for reconstruction of bone and a wide variety of dental, orthopedic. Both human and bovine collagen is used as dermal fillers for treatment of wrinkles
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Endoplasmic reticulum
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The endoplasmic reticulum is a type of organelle in eukaryotic cells that forms an interconnected network of flattened, membrane-enclosed sacs or tube-like structures known as cisternae. The membranes of the ER are continuous with the nuclear membrane. The endoplasmic reticulum occurs in most types of cells, including Giardia. There are two types of endoplasmic reticulum, rough and smooth, the outer face of the rough endoplasmic reticulum is studded with ribosomes that are the sites of protein synthesis. The rough endoplasmic reticulum is especially prominent in such as hepatocytes. The smooth endoplasmic reticulum lacks ribosomes and functions in lipid manufacture and metabolism, the production of steroid hormones, the smooth ER is especially abundant in mammalian liver and gonad cells. The lacy membranes of the endoplasmic reticulum were first seen in 1945 using electron microscopy, the lacy membranes of the endoplasmic reticulum were first seen in 1945 by Keith R. Porter, Albert Claude, Brody Meskers and Ernest F. Fullam, using electron microscopy. The word reticulum, which network, was applied to describe this fabric of membranes. The general structure of the reticulum is a network of membranes called cisternae. These sac-like structures are held together by the cytoskeleton, the phospholipid membrane encloses the cisternal space, which is continuous with the perinuclear space but separate from the cytosol. The functions of the reticulum can be summarized as the synthesis and export of proteins and membrane lipids. The quantity of both rough and smooth endoplasmic reticulum in a cell can slowly interchange from one type to the other, transformation can include embedding of new proteins in membrane as well as structural changes. Changes in protein content may occur without noticeable structural changes, the surface of the rough endoplasmic reticulum is studded with protein-manufacturing ribosomes giving it a rough appearance. The binding site of the ribosome on the endoplasmic reticulum is the translocon. However, the ribosomes are not a part of this organelles structure as they are constantly being bound. A ribosome only binds to the RER once a specific protein-nucleic acid complex forms in the cytosol and this special complex forms when a free ribosome begins translating the mRNA of a protein destined for the secretory pathway. The first 5-30 amino acids polymerized encode a signal peptide, a message that is recognized. Translation pauses and the complex binds to the RER translocon where translation continues with the nascent protein forming into the RER lumen and/or membrane
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Golgi apparatus
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The Golgi apparatus, also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. It was identified in 1897 by the Italian scientist Camillo Golgi, part of the cellular endomembrane system, the Golgi apparatus packages proteins into membrane-bound vesicles inside the cell before the vesicles are sent to their destination. The Golgi apparatus resides at the intersection of the secretory, lysosomal, owing to its large size and distinctive structure, the Golgi apparatus was one of the first organelles to be discovered and observed in detail. It was discovered in 1898 by Italian physician Camillo Golgi during an investigation of the nervous system, after first observing it under his microscope, he termed the structure the internal reticular apparatus. Some doubted the discovery at first, arguing that the appearance of the structure was merely an illusion created by the observation technique used by Golgi. With the development of modern microscopes in the 20th century, the discovery was confirmed, early references to the Golgi referred to it by various names including the Golgi–Holmgren apparatus, Golgi–Holmgren ducts, and Golgi–Kopsch apparatus. The term Golgi apparatus was used in 1910 and first appeared in the literature in 1913. Among eukaryotes, the localization of the Golgi apparatus differs. In mammals, a single Golgi apparatus complex is located near the cell nucleus. Tubular connections are responsible for linking the stacks together, localization and tubular connections of the Golgi apparatus are dependent on microtubules. If microtubules are experimentally depolymerized, then the Golgi apparatus loses connections, in yeast, multiple Golgi apparatuses are scattered throughout the cytoplasm. In plants, Golgi stacks are not concentrated at the centrosomal region, organization of the plant Golgi depends on actin cables and not microtubules. The common feature among Golgi is that they are adjacent to endoplasmic reticulum exit sites, in most eukaryotes, the Golgi apparatus is made up of a series of compartments consisting of two main networks, the cis Golgi network and the trans Golgi network. The CGN is a collection of fused, flattened membrane-enclosed disks known as cisternae, a mammalian cell typically contains 40 to 100 stacks. Between four and eight cisternae are usually present in a stack, however and this collection of cisternae is broken down into cis, medial, and trans compartments. The TGN is the final structure, from which proteins are packaged into vesicles destined to lysosomes, secretory vesicles. The TGN is usually positioned adjacent to the stacks of the Golgi apparatus, the TGN may act as an early endosome in yeast and plants. There are structural and organizational differences in the Golgi apparatus among eukaryotes, in some yeasts, Golgi stacking is not observed
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Secretion
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Secretion is the movement of material from one point to another, e. g. secreted chemical substance from a cell or gland. In contrast, excretion, is the removal of certain substances or waste products from a cell or organism, the classical mechanism of cell secretion is via secretory portals at the cell plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structure at the plasma membrane. Secretion in bacterial species means the transport or translocation of molecules for example, proteins. Secretion is an important mechanism in bacterial functioning and operation in their natural surrounding environment for adaptation. Eukaryotic cells, including human cells, have a highly evolved process of secretion, proteins targeted for the outside are synthesized by ribosomes docked to the rough endoplasmic reticulum. As they are synthesized, these proteins translocate into the ER lumen, where they are glycosylated, misfolded proteins are usually identified here and retrotranslocated by ER-associated degradation to the cytosol, where they are degraded by a proteasome. The vesicles containing the properly folded proteins then enter the Golgi apparatus, in the Golgi apparatus, the glycosylation of the proteins is modified and further posttranslational modifications, including cleavage and functionalization, may occur. The proteins are then moved into secretory vesicles which travel along the cytoskeleton to the edge of the cell, more modification can occur in the secretory vesicles. Eventually, there is vesicle fusion with the membrane at a structure called the porosome, in a process called exocytosis. Strict biochemical control is maintained over this sequence by usage of a pH gradient, the pH of the cytosol is 7.4, the ERs pH is 7.0, and the cis-golgi has a pH of 6.5. Secretory vesicles have pHs ranging between 5.0 and 6.0, some secretory vesicles evolve into lysosomes, which have a pH of 4.8, there are many proteins like FGF1, FGF2, interleukin-1 etc. which do not have a signal sequence. They do not use the classical ER-golgi pathway and these are secreted through various nonclassical pathways. At least four nonclassical protein secretion pathways have been described, many human cell types have the ability to be secretory cells. They have a well-developed endoplasmic reticulum and Golgi apparatus to fulfill their function, meibomian glands in the eyelid secrete sebum to lubricate and protect the eye. Secretion is not unique to eukaryotes alone, it is present in bacteria, ATP binding cassette type transporters are common to all the three domains of life. Some secreted proteins are translocated across the membrane by the Sec translocon. Others are translocated across the membrane by the twin-arginine translocation pathway
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