page:  = Protein = 
   
   Proteins ( / ˈproʊˌtiːnz / or / ˈproʊti.ᵻnz / ) 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 , and transporting molecules from one location to another . Proteins differ from one another primarily in their sequence of amino acids , which is dictated by the nucleotide sequence of their genes , and which usually results in protein folding into a specific three @-@ dimensional structure that determines its activity . 
   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 and adjacent amino acid residues . 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 genetic code specifies 20 standard amino acids ; however , in certain organisms the genetic code can include selenocysteine and — in certain archaea — pyrrolysine . Shortly after or even during synthesis , the residues in a protein are often chemically modified by post @-@ translational modification , which alters the physical and chemical properties , folding , stability , activity , and ultimately , the function of the proteins . 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 certain period of time and are then degraded and recycled by the cell 's machinery through the process of protein turnover . A protein 's lifespan is measured in terms of its half @-@ life and covers a wide range . 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 either 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 and participate in virtually every process within cells . 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 , which form a system of scaffolding that maintains cell shape . 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 . 
   Proteins may be purified from other cellular components using a variety of techniques such as ultracentrifugation , precipitation , electrophoresis , and chromatography ; the advent of genetic engineering has made possible a number of methods to facilitate purification . Methods commonly used to study protein structure and function include immunohistochemistry , site @-@ directed mutagenesis , X @-@ ray crystallography , nuclear magnetic resonance and mass spectrometry . 
   
   = = Biochemistry = = 
   
   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 basic structure as it contains an unusual ring to the N @-@ end amine group , which forces the CO – NH amide moiety into a fixed conformation . The side chains of the standard amino acids , detailed in the list of standard amino acids , have a great variety of chemical structures and properties ; it is the combined effect of all of the amino acid side chains in a protein that ultimately determines its three @-@ dimensional structure and its chemical reactivity . The amino acids in a polypeptide chain are linked by peptide bonds . Once linked in the protein chain , an individual amino acid is called a residue , and the linked series of carbon , nitrogen , and oxygen atoms are known as the main chain or protein backbone . 
   The peptide bond has two resonance forms that contribute some double @-@ bond character and inhibit rotation around its axis , so that the alpha carbons are roughly coplanar . The other two dihedral angles in the peptide bond determine the local shape assumed by the protein backbone . The end of the protein with a free carboxyl group is known as the C @-@ terminus or carboxy terminus , whereas the end with a free amino group is known as the N @-@ terminus or amino terminus . The words protein , polypeptide , and peptide are a little ambiguous and can overlap in meaning . Protein is generally used to refer to the complete biological molecule in a stable conformation , whereas peptide is generally reserved for a short amino acid oligomers often lacking a stable three @-@ dimensional structure . However , the boundary between the two is not well defined and usually lies near 20 – 30 residues . Polypeptide can refer to any single linear chain of amino acids , usually regardless of length , but often implies an absence of a defined conformation . 
   
   = = = Abundance in cells = = = 
   
   It has been estimated that average @-@ sized bacteria contain about 2 million proteins per cell ( e.g. E. coli and Staphylococcus aureus ) . Smaller bacteria , such as Mycoplasma or spirochetes contain fewer molecules , namely on the order of 50 @,@ 000 to 1 million . By contrast , eukaryotic cells are larger and thus contain much more protein . For instance , yeast cells were estimated to contain about 50 million proteins and human cells on the order of 1 to 3 billion . Note that bacterial genomes encode about 10 times fewer proteins than humans ( e.g. small bacteria ~ 1 @,@ 000 , E. coli : ~ 4 @,@ 000 , yeast : ~ 6 @,@ 000 , human : ~ 20 @,@ 000 ) . 
   Importantly , the concentration of individual proteins ranges from a few molecules per cell to hundreds of thousands . In fact , about a third of all proteins is not produced in most cells or only induced under certain circumstances . For instance , of the 20 @,@ 000 or so proteins encoded by the human genome only 6 @,@ 000 are detected in lymphoblastoid cells . 
   
   = = Synthesis = = 
   
   
   = = = Biosynthesis = = = 
   
   Proteins are assembled from amino acids using information encoded in genes . Each protein has its own unique amino acid sequence that is specified by the nucleotide sequence of the gene encoding this protein . The genetic code is a set of three @-@ nucleotide sets called codons and each three @-@ nucleotide combination designates an amino acid , for example AUG ( adenine @-@ uracil @-@ guanine ) is the code for methionine . Because DNA contains four nucleotides , the total number of possible codons is 64 ; hence , there is some redundancy in the genetic code , with some amino acids specified by more than one codon . Genes encoded in DNA are first transcribed into pre @-@ messenger RNA ( mRNA ) by proteins such as RNA polymerase . Most organisms then process the pre @-@ mRNA ( also known as a primary transcript ) using various forms of Post @-@ transcriptional modification to form the mature mRNA , which is then used as a template for protein synthesis by the ribosome . In prokaryotes the mRNA may either be used as soon as it is produced , or be bound by a ribosome after having moved away from the nucleoid . In contrast , eukaryotes make mRNA in the cell nucleus and then translocate it across the nuclear membrane into the cytoplasm , where protein synthesis then takes place . The rate of protein synthesis is higher in prokaryotes than eukaryotes and can reach up to 20 amino acids per second . 
   The process of synthesizing a protein from an mRNA template is known as translation . The mRNA is loaded onto the ribosome and is read three nucleotides at a time by matching each codon to its base pairing anticodon located on a transfer RNA molecule , which carries the amino acid corresponding to the codon it recognizes . The enzyme aminoacyl tRNA synthetase " charges " the tRNA molecules with the correct amino acids . The growing polypeptide is often termed the nascent chain . Proteins are always biosynthesized from N @-@ terminus to C @-@ terminus . 
   The size of a synthesized protein can be measured by the number of amino acids it contains and by its total molecular mass , which is normally reported in units of daltons ( synonymous with atomic mass units ) , or the derivative unit kilodalton ( kDa ) . Yeast proteins are on average 466 amino acids long and 53 kDa in mass . The largest known proteins are the titins , a component of the muscle sarcomere , with a molecular mass of almost 3 @,@ 000 kDa and a total length of almost 27 @,@ 000 amino acids . 
   
   = = = Chemical synthesis = = = 
   
   Short proteins can also be synthesized chemically by a family of methods known as peptide synthesis , which rely on organic synthesis techniques such as chemical ligation to produce peptides in high yield . Chemical synthesis allows for the introduction of non @-@ natural amino acids into polypeptide chains , such as attachment of fluorescent probes to amino acid side chains . These methods are useful in laboratory biochemistry and cell biology , though generally not for commercial applications . Chemical synthesis is inefficient for polypeptides longer than about 300 amino acids , and the synthesized proteins may not readily assume their native tertiary structure . Most chemical synthesis methods proceed from C @-@ terminus to N @-@ terminus , opposite the biological reaction . 
   
   = = Structure = = 
   
   Most proteins fold into unique 3 @-@ dimensional structures . The shape into which a protein naturally folds is known as its native conformation . Although many proteins can fold unassisted , simply through the chemical properties of their amino acids , others require the aid of molecular chaperones to fold into their native states . Biochemists often refer to four distinct aspects of a protein 's structure : 
   Primary structure : the amino acid sequence . A protein is a polyamide . 
   Secondary structure : regularly repeating local structures stabilized by hydrogen bonds . The most common examples are the α @-@ helix , β @-@ sheet and turns . Because secondary structures are local , many regions of different secondary structure can be present in the same protein molecule . 
   Tertiary structure : the overall shape of a single protein molecule ; the spatial relationship of the secondary structures to one another . Tertiary structure is generally stabilized by nonlocal interactions , most commonly the formation of a hydrophobic core , but also through salt bridges , hydrogen bonds , disulfide bonds , and even posttranslational modifications . The term " tertiary structure " is often used as synonymous with the term fold . The tertiary structure is what controls the basic function of the protein . 
   Quaternary structure : the structure formed by several protein molecules ( polypeptide chains ) , usually called protein subunits in this context , which function as a single protein complex . 
   Proteins are not entirely rigid molecules . In addition to these levels of structure , proteins may shift between several related structures while they perform their functions . In the context of these functional rearrangements , these tertiary or quaternary structures are usually referred to as " conformations " , and transitions between them are called conformational changes . Such changes are often induced by the binding of a substrate molecule to an enzyme 's active site , or the physical region of the protein that participates in chemical catalysis . In solution proteins also undergo variation in structure through thermal vibration and the collision with other molecules . 
   Proteins can be informally divided into three main classes , which correlate with typical tertiary structures : globular proteins , fibrous proteins , and membrane proteins . Almost all globular proteins are soluble and many are enzymes . Fibrous proteins are often structural , such as collagen , the major component of connective tissue , or keratin , the protein component of hair and nails . Membrane proteins often serve as receptors or provide channels for polar or charged molecules to pass through the cell membrane . 
   A special case of intramolecular hydrogen bonds within proteins , poorly shielded from water attack and hence promoting their own dehydration , are called dehydrons . 
   
   = = = Structure determination = = = 
   
   Discovering the tertiary structure of a protein , or the quaternary structure of its complexes , can provide important clues about how the protein performs its function . Common experimental methods of structure determination include X @-@ ray crystallography and NMR spectroscopy , both of which can produce information at atomic resolution . However , NMR experiments are able to provide information from which a subset of distances between pairs of atoms can be estimated , and the final possible conformations for a protein are determined by solving a distance geometry problem . Dual polarisation interferometry is a quantitative analytical method for measuring the overall protein conformation and conformational changes due to interactions or other stimulus . Circular dichroism is another laboratory technique for determining internal β @-@ sheet / α @-@ helical composition of proteins . Cryoelectron microscopy is used to produce lower @-@ resolution structural information about very large protein complexes , including assembled viruses ; a variant known as electron crystallography can also produce high @-@ resolution information in some cases , especially for two @-@ dimensional crystals of membrane proteins . Solved structures are usually deposited in the Protein Data Bank ( PDB ) , a freely available resource from which structural data about thousands of proteins can be obtained in the form of Cartesian coordinates for each atom in the protein . 
   Many more gene sequences are known than protein structures . Further , the set of solved structures is biased toward proteins that can be easily subjected to the conditions required in X @-@ ray crystallography , one of the major structure determination methods . In particular , globular proteins are comparatively easy to crystallize in preparation for X @-@ ray crystallography . Membrane proteins , by contrast , are difficult to crystallize and are underrepresented in the PDB . Structural genomics initiatives have attempted to remedy these deficiencies by systematically solving representative structures of major fold classes . Protein structure prediction methods attempt to provide a means of generating a plausible structure for proteins whose structures have not been experimentally determined . 
   
   = = Cellular functions = = 
   
   Proteins are the chief actors within the cell , said to be carrying out the duties specified by the information encoded in genes . With the exception of certain types of RNA , most other biological molecules are relatively inert elements upon which proteins act . Proteins make up half the dry weight of an Escherichia coli cell , whereas other macromolecules such as DNA and RNA make up only 3 % and 20 % , respectively . The set of proteins expressed in a particular cell or cell type is known as its proteome . 
   The chief characteristic of proteins that also allows their diverse set of functions is their ability to bind other molecules specifically and tightly . The region of the protein responsible for binding another molecule is known as the binding site and is often a depression or " pocket " on the molecular surface . This binding ability is mediated by the tertiary structure of the protein , which defines the binding site pocket , and by the chemical properties of the surrounding amino acids ' side chains . Protein binding can be extraordinarily tight and specific ; for example , the ribonuclease inhibitor protein binds to human angiogenin with a sub @-@ femtomolar dissociation constant ( < 10 − 15 M ) but does not bind at all to its amphibian homolog onconase ( > 1 M ) . Extremely minor chemical changes such as the addition of a single methyl group to a binding partner can sometimes suffice to nearly eliminate binding ; for example , the aminoacyl tRNA synthetase specific to the amino acid valine discriminates against the very similar side chain of the amino acid isoleucine . 
   Proteins can bind to other proteins as well as to small @-@ molecule substrates . When proteins bind specifically to other copies of the same molecule , they can oligomerize to form fibrils ; this process occurs often in structural proteins that consist of globular monomers that self @-@ associate to form rigid fibers . Protein – protein interactions also regulate enzymatic activity , control progression through the cell cycle , and allow the assembly of large protein complexes that carry out many closely related reactions with a common biological function . Proteins can also bind to , or even be integrated into , cell membranes . The ability of binding partners to induce conformational changes in proteins allows the construction of enormously complex signaling networks . Importantly , as interactions between proteins are reversible , and depend heavily on the availability of different groups of partner proteins to form aggregates that are capable to carry out discrete sets of function , study of the interactions between specific proteins is a key to understand important aspects of cellular function , and ultimately the properties that distinguish particular cell types . 
   
   = = = Enzymes = = = 
   
   The best @-@ known role of proteins in the cell is as enzymes , which catalyse chemical reactions . Enzymes are usually highly specific and accelerate only one or a few chemical reactions . Enzymes carry out most of the reactions involved in metabolism , as well as manipulating DNA in processes such as DNA replication , DNA repair , and transcription . Some enzymes act on other proteins to add or remove chemical groups in a process known as posttranslational modification . About 4 @,@ 000 reactions are known to be catalysed by enzymes . The rate acceleration conferred by enzymatic catalysis is often enormous — as much as 1017 @-@ fold increase in rate over the uncatalysed reaction in the case of orotate decarboxylase ( 78 million years without the enzyme , 18 milliseconds with the enzyme ) . 
   The molecules bound and acted upon by enzymes are called substrates . Although enzymes can consist of hundreds of amino acids , it is usually only a small fraction of the residues that come in contact with the substrate , and an even smaller fraction — three to four residues on average — that are directly involved in catalysis . The region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site . 
   Dirigent proteins are members of a class of proteins that dictate the stereochemistry of a compound synthesized by other enzymes . 
   
   = = = Cell signaling and ligand binding = = = 
   
   Many proteins are involved in the process of cell signaling and signal transduction . Some proteins , such as insulin , are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant tissues . Others are membrane proteins that act as receptors whose main function is to bind a signaling molecule and induce a biochemical response in the cell . Many receptors have a binding site exposed on the cell surface and an effector domain within the cell , which may have enzymatic activity or may undergo a conformational change detected by other proteins within the cell . 
   Antibodies are protein components of an adaptive immune system whose main function is to bind antigens , or foreign substances in the body , and target them for destruction . Antibodies can be secreted into the extracellular environment or anchored in the membranes of specialized B cells known as plasma cells . Whereas enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction , antibodies have no such constraints . An antibody 's binding affinity to its target is extraordinarily high . 
   Many ligand transport proteins bind particular small biomolecules and transport them to other locations in the body of a multicellular organism . These proteins must have a high binding affinity when their ligand is present in high concentrations , but must also release the ligand when it is present at low concentrations in the target tissues . The canonical example of a ligand @-@ binding protein is haemoglobin , which transports oxygen from the lungs to other organs and tissues in all vertebrates and has close homologs in every biological kingdom . Lectins are sugar @-@ binding proteins which are highly specific for their sugar moieties . Lectins typically play a role in biological recognition phenomena involving cells and proteins . Receptors and hormones are highly specific binding proteins . 
   Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions . The membrane alone has a hydrophobic core through which polar or charged molecules cannot diffuse . Membrane proteins contain internal channels that allow such molecules to enter and exit the cell . Many ion channel proteins are specialized to select for only a particular ion ; for example , potassium and sodium channels often discriminate for only one of the two ions . 
   
   = = = Structural proteins = = = 
   
   Structural proteins confer stiffness and rigidity to otherwise @-@ fluid biological components . Most structural proteins are fibrous proteins ; for example , collagen and elastin are critical components of connective tissue such as cartilage , and keratin is found in hard or filamentous structures such as hair , nails , feathers , hooves , and some animal shells . Some globular proteins can also play structural functions , for example , actin and tubulin are globular and soluble as monomers , but polymerize to form long , stiff fibers that make up the cytoskeleton , which allows the cell to maintain its shape and size . 
   Other proteins that serve structural functions are motor proteins such as myosin , kinesin , and dynein , which are capable of generating mechanical forces . These proteins are crucial for cellular motility of single celled organisms and the sperm of many multicellular organisms which reproduce sexually . They also generate the forces exerted by contracting muscles and play essential roles in intracellular transport . 
   
   = = Methods of study = = 
   
   The activities and structures of proteins may be examined in vitro , in vivo , and in silico . In vitro studies of purified proteins in controlled environments are useful for learning how a protein carries out its function : for example , enzyme kinetics studies explore the chemical mechanism of an enzyme 's catalytic activity and its relative affinity for various possible substrate molecules . By contrast , in vivo experiments can provide information about the physiological role of a protein in the context of a cell or even a whole organism . In silico studies use computational methods to study proteins . 
   
   = = = Protein purification = = = 
   
   To perform in vitro analysis , a protein must be purified away from other cellular components . This process usually begins with cell lysis , in which a cell 's membrane is disrupted and its internal contents released into a solution known as a crude lysate . The resulting mixture can be purified using ultracentrifugation , which fractionates the various cellular components into fractions containing soluble proteins ; membrane lipids and proteins ; cellular organelles , and nucleic acids . Precipitation by a method known as salting out can concentrate the proteins from this lysate . Various types of chromatography are then used to isolate the protein or proteins of interest based on properties such as molecular weight , net charge and binding affinity . The level of purification can be monitored using various types of gel electrophoresis if the desired protein 's molecular weight and isoelectric point are known , by spectroscopy if the protein has distinguishable spectroscopic features , or by enzyme assays if the protein has enzymatic activity . Additionally , proteins can be isolated according their charge using electrofocusing . 
   For natural proteins , a series of purification steps may be necessary to obtain protein sufficiently pure for laboratory applications . To simplify this process , genetic engineering is often used to add chemical features to proteins that make them easier to purify without affecting their structure or activity . Here , a " tag " consisting of a specific amino acid sequence , often a series of histidine residues ( a " His @-@ tag " ) , is attached to one terminus of the protein . As a result , when the lysate is passed over a chromatography column containing nickel , the histidine residues ligate the nickel and attach to the column while the untagged components of the lysate pass unimpeded . A number of different tags have been developed to help researchers purify specific proteins from complex mixtures . 
   
   = = = Cellular localization = = = 
   
   The study of proteins in vivo is often concerned with the synthesis and localization of the protein within the cell . Although many intracellular proteins are synthesized in the cytoplasm and membrane @-@ bound or secreted proteins in the endoplasmic reticulum , the specifics of how proteins are targeted to specific organelles or cellular structures is often unclear . A useful technique for assessing cellular localization uses genetic engineering to express in a cell a fusion protein or chimera consisting of the natural protein of interest linked to a " reporter " such as green fluorescent protein ( GFP ) . The fused protein 's position within the cell can be cleanly and efficiently visualized using microscopy , as shown in the figure opposite . 
   Other methods for elucidating the cellular location of proteins requires the use of known compartmental markers for regions such as the ER , the Golgi , lysosomes or vacuoles , mitochondria , chloroplasts , plasma membrane , etc . With the use of fluorescently tagged versions of these markers or of antibodies to known markers , it becomes much simpler to identify the localization of a protein of interest . For example , indirect immunofluorescence will allow for fluorescence colocalization and demonstration of location . Fluorescent dyes are used to label cellular compartments for a similar purpose . 
   Other possibilities exist , as well . For example , immunohistochemistry usually utilizes an antibody to one or more proteins of interest that are conjugated to enzymes yielding either luminescent or chromogenic signals that can be compared between samples , allowing for localization information . Another applicable technique is cofractionation in sucrose ( or other material ) gradients using isopycnic centrifugation . While this technique does not prove colocalization of a compartment of known density and the protein of interest , it does increase the likelihood , and is more amenable to large @-@ scale studies . 
   Finally , the gold @-@ standard method of cellular localization is immunoelectron microscopy . This technique also uses an antibody to the protein of interest , along with classical electron microscopy techniques . The sample is prepared for normal electron microscopic examination , and then treated with an antibody to the protein of interest that is conjugated to an extremely electro @-@ dense material , usually gold . This allows for the localization of both ultrastructural details as well as the protein of interest . 
   Through another genetic engineering application known as site @-@ directed mutagenesis , researchers can alter the protein sequence and hence its structure , cellular localization , and susceptibility to regulation . This technique even allows the incorporation of unnatural amino acids into proteins , using modified tRNAs , and may allow the rational design of new proteins with novel properties . 
   
   = = = Proteomics = = = 
   
   The total complement of proteins present at a time in a cell or cell type is known as its proteome , and the study of such large @-@ scale data sets defines the field of proteomics , named by analogy to the related field of genomics . Key experimental techniques in proteomics include 2D electrophoresis , which allows the separation of a large number of proteins , mass spectrometry , which allows rapid high @-@ throughput identification of proteins and sequencing of peptides ( most often after in @-@ gel digestion ) , protein microarrays , which allow the detection of the relative levels of a large number of proteins present in a cell , and two @-@ hybrid screening , which allows the systematic exploration of protein – protein interactions . The total complement of biologically possible such interactions is known as the interactome . A systematic attempt to determine the structures of proteins representing every possible fold is known as structural genomics . 
   
   = = = Bioinformatics = = = 
   
   A vast array of computational methods have been developed to analyze the structure , function , and evolution of proteins . 
   The development of such tools has been driven by the large amount of genomic and proteomic data available for a variety of organisms , including the human genome . It is simply impossible to study all proteins experimentally , hence only a few are subjected to laboratory experiments while computational tools are used to extrapolate to similar proteins . Such homologous proteins can be efficiently identified in distantly related organisms by sequence alignment . Genome and gene sequences can be searched by a variety of tools for certain properties . Sequence profiling tools can find restriction enzyme sites , open reading frames in nucleotide sequences , and predict secondary structures . Phylogenetic trees can be constructed and evolutionary hypotheses developed using special software like ClustalW regarding the ancestry of modern organisms and the genes they express . The field of bioinformatics is now indispensable for the analysis of genes and proteins . 
   
   = = = = Structure prediction and simulation = = = = 
   
   Complementary to the field of structural genomics , protein structure prediction seeks to develop efficient ways to provide plausible models for proteins whose structures have not yet been determined experimentally . The most successful type of structure prediction , known as homology modeling , relies on the existence of a " template " structure with sequence similarity to the protein being modeled ; structural genomics ' goal is to provide sufficient representation in solved structures to model most of those that remain . Although producing accurate models remains a challenge when only distantly related template structures are available , it has been suggested that sequence alignment is the bottleneck in this process , as quite accurate models can be produced if a " perfect " sequence alignment is known . Many structure prediction methods have served to inform the emerging field of protein engineering , in which novel protein folds have already been designed . A more complex computational problem is the prediction of intermolecular interactions , such as in molecular docking and protein – protein interaction prediction . 
   The processes of protein folding and binding can be simulated using such technique as molecular mechanics , in particular , molecular dynamics and Monte Carlo , which increasingly take advantage of parallel and distributed computing ( Folding @ home project ; molecular modeling on GPU ) . The folding of small α @-@ helical protein domains such as the villin headpiece and the HIV accessory protein have been successfully simulated in silico , and hybrid methods that combine standard molecular dynamics with quantum mechanics calculations have allowed exploration of the electronic states of rhodopsins . 
   
   = = = = Protein disorder and unstructure prediction = = = = 
   
   Many proteins ( in Eucaryota ~ 33 % ) contain large unstructured but biologically functional segments and can be classified as intrinsically disordered proteins . Predicting and analysing protein disorder is , therefore , an important part of protein structure characterisation . 
   
   = = Nutrition = = 
   
   Most microorganisms and plants can biosynthesize all 20 standard amino acids , while animals ( including humans ) must obtain some of the amino acids from the diet . The amino acids that an organism cannot synthesize on its own are referred to as essential amino acids . Key enzymes that synthesize certain amino acids are not present in animals — such as aspartokinase , which catalyses the first step in the synthesis of lysine , methionine , and threonine from aspartate . If amino acids are present in the environment , microorganisms can conserve energy by taking up the amino acids from their surroundings and downregulating their biosynthetic pathways . 
   In animals , amino acids are obtained through the consumption of foods containing protein . Ingested proteins are then broken down into amino acids through digestion , which typically involves denaturation of the protein through exposure to acid and hydrolysis by enzymes called proteases . Some ingested amino acids are used for protein biosynthesis , while others are converted to glucose through gluconeogenesis , or fed into the citric acid cycle . This use of protein as a fuel is particularly important under starvation conditions as it allows the body 's own proteins to be used to support life , particularly those found in muscle . Amino acids are also an important dietary source of nitrogen . 
   
   = = History and etymology = = 
   
   Proteins were recognized as a distinct class of biological molecules in the eighteenth century by Antoine Fourcroy and others , distinguished by the molecules ' ability to coagulate or flocculate under treatments with heat or acid . Noted examples at the time included albumin from egg whites , blood serum albumin , fibrin , and wheat gluten . 
   Proteins were first described by the Dutch chemist Gerardus Johannes Mulder and named by the Swedish chemist Jöns Jacob Berzelius in 1838 . Mulder carried out elemental analysis of common proteins and found that nearly all proteins had the same empirical formula , C400H620N100O120P1S1 . He came to the erroneous conclusion that they might be composed of a single type of ( very large ) molecule . The term " protein " to describe these molecules was proposed by Mulder 's associate Berzelius ; protein is derived from the Greek word πρώτειος ( proteios ) , meaning " primary " , " in the lead " , or " standing in front " , + -in . Mulder went on to identify the products of protein degradation such as the amino acid leucine for which he found a ( nearly correct ) molecular weight of 131 Da . 
   Early nutritional scientists such as the German Carl von Voit believed that protein was the most important nutrient for maintaining the structure of the body , because it was generally believed that " flesh makes flesh . " Karl Heinrich Ritthausen extended known protein forms with the identification of glutamic acid . At the Connecticut Agricultural Experiment Station a detailed review of the vegetable proteins was compiled by Thomas Burr Osborne . Working with Lafayette Mendel and applying Liebig 's law of the minimum in feeding laboratory rats , the nutritionally essential amino acids were established . The work was continued and communicated by William Cumming Rose . The understanding of proteins as polypeptides came through the work of Franz Hofmeister and Hermann Emil Fischer . The central role of proteins as enzymes in living organisms was not fully appreciated until 1926 , when James B. Sumner showed that the enzyme urease was in fact a protein . 
   The difficulty in purifying proteins in large quantities made them very difficult for early protein biochemists to study . Hence , early studies focused on proteins that could be purified in large quantities , e.g. , those of blood , egg white , various toxins , and digestive / metabolic enzymes obtained from slaughterhouses . In the 1950s , the Armour Hot Dog Co. purified 1 kg of pure bovine pancreatic ribonuclease A and made it freely available to scientists ; this gesture helped ribonuclease A become a major target for biochemical study for the following decades . 
   Linus Pauling is credited with the successful prediction of regular protein secondary structures based on hydrogen bonding , an idea first put forth by William Astbury in 1933 . Later work by Walter Kauzmann on denaturation , based partly on previous studies by Kaj Linderstrøm @-@ Lang , contributed an understanding of protein folding and structure mediated by hydrophobic interactions . 
   The first protein to be sequenced was insulin , by Frederick Sanger , in 1949 . Sanger correctly determined the amino acid sequence of insulin , thus conclusively demonstrating that proteins consisted of linear polymers of amino acids rather than branched chains , colloids , or cyclols . He won the Nobel Prize for this achievement in 1958 . 
   The first protein structures to be solved were hemoglobin and myoglobin , by Max Perutz and Sir John Cowdery Kendrew , respectively , in 1958 . As of 2016 , the Protein Data Bank has over 115 @,@ 000 atomic @-@ resolution structures of proteins . In more recent times , cryo @-@ electron microscopy of large macromolecular assemblies and computational protein structure prediction of small protein domains are two methods approaching atomic resolution . 
   
   = = Textbooks = = 
   
   
   = = = Databases and projects = = = 
   
   The Protein Naming Utility 
   Human Protein Atlas 
   NCBI Entrez Protein database 
   NCBI Protein Structure database 
   Human Protein Reference Database 
   Human Proteinpedia 
   Folding @ Home ( Stanford University ) 
   Comparative Toxicogenomics Database curates protein – chemical interactions , as well as gene / protein – disease relationships and chemical @-@ disease relationships . 
   Bioinformatic Harvester A Meta search engine ( 29 databases ) for gene and protein information . 
   Protein Databank in Europe ( see also PDBeQuips , short articles and tutorials on interesting PDB structures ) 
   Research Collaboratory for Structural Bioinformatics ( see also Molecule of the Month , presenting short accounts on selected proteins from the PDB ) 
   Proteopedia – Life in 3D : rotatable , zoomable 3D model with wiki annotations for every known protein molecular structure . 
   UniProt the Universal Protein Resource 
   neXtProt – Exploring the universe of human proteins : human @-@ centric protein knowledge resource 
   Multi @-@ Omics Profiling Expression Database : MOPED human and model organism protein / gene knowledge and expression data 
   
   = = = Tutorials and educational websites = = = 
   
   " An Introduction to Proteins " from HOPES ( Huntington 's Disease Outreach Project for Education at Stanford ) 
   Proteins : Biogenesis to Degradation – The Virtual Library of Biochemistry and Cell Biology 
   Alphabet of Protein Structures 
   