<p><strong>Proteins</strong> are large <a title="Organic compound" href="http://en.wikipedia.org/wiki/Organic_compound">organic compounds</a> made of <a title="Amino acid" href="http://en.wikipedia.org/wiki/Amino_acid">amino acids</a> arranged in a linear chain and joined together by <a title="Peptide bond" href="http://en.wikipedia.org/wiki/Peptide_bond">peptide bonds</a> between the <a title="Carboxyl" href="http://en.wikipedia.org/wiki/Carboxyl">carboxyl</a> and <a title="Amino" href="http://en.wikipedia.org/wiki/Amino">amino</a> groups of adjacent amino acid <a title="Residues" href="http://en.wikipedia.org/wiki/Residues">residues</a>. The sequence of amino acids in a protein is defined by a <a title="Gene" href="http://en.wikipedia.org/wiki/Gene">gene</a> and encoded in the <a title="Genetic code" href="http://en.wikipedia.org/wiki/Genetic_code">genetic code</a>. Although this genetic code specifies 20 &quot;standard&quot; amino acids, the residues in a protein are often chemically altered in <a title="Post-translational modification" href="http://en.wikipedia.org/wiki/Post-translational_modification">post-translational modification</a>: either before the protein can function in the <a title="Cell (biology)" href="http://en.wikipedia.org/wiki/Cell_%28biology%29">cell</a>, or as part of control mechanisms. Proteins can also work together to achieve a particular function, and they often associate to form stable <a title="Protein complex" href="http://en.wikipedia.org/wiki/Protein_complex">complexes</a>.</p><p>Like other biological <a title="Macromolecules" href="http://en.wikipedia.org/wiki/Macromolecules">macromolecules</a> such as <a title="Polysaccharide" href="http://en.wikipedia.org/wiki/Polysaccharide">polysaccharides</a> and <a title="Nucleic acid" href="http://en.wikipedia.org/wiki/Nucleic_acid">nucleic acids</a>, proteins are essential parts of all living organisms and participate in every process within <a title="Cell (biology)" href="http://en.wikipedia.org/wiki/Cell_%28biology%29">cells</a>. Many proteins are <a title="Enzyme" href="http://en.wikipedia.org/wiki/Enzyme">enzymes</a> that <a title="Catalysis" href="http://en.wikipedia.org/wiki/Catalysis">catalyze</a> biochemical reactions, and are vital to <a title="Metabolism" href="http://en.wikipedia.org/wiki/Metabolism">metabolism</a>. Other proteins have structural or mechanical functions, such as the proteins in the <a title="Cytoskeleton" href="http://en.wikipedia.org/wiki/Cytoskeleton">cytoskeleton</a>, which forms a system of <a title="Scaffolding" href="http://en.wikipedia.org/wiki/Scaffolding">scaffolding</a> that maintains cell shape. Proteins are also important in <a title="Cell signaling" href="http://en.wikipedia.org/wiki/Cell_signaling">cell signaling</a>, <a title="Antibody" href="http://en.wikipedia.org/wiki/Antibody">immune responses</a>, <a title="Cell adhesion" href="http://en.wikipedia.org/wiki/Cell_adhesion"><font color="#810081">cell adhesion</font></a>, and the <a title="Cell cycle" href="http://en.wikipedia.org/wiki/Cell_cycle">cell cycle</a>. Protein is also a necessary component in our diet, since animals cannot synthesise all the amino acids and must obtain <a title="Essential amino acid" href="http://en.wikipedia.org/wiki/Essential_amino_acid">essential amino acids</a> from food. Through the process of <a title="Digestion" href="http://en.wikipedia.org/wiki/Digestion">digestion</a>, animals break down ingested protein into free amino acids that can be used for <a title="Protein biosynthesis" href="http://en.wikipedia.org/wiki/Protein_biosynthesis">protein synthesis</a>.</p><p>The word <em>protein</em> comes from the <a title="Greek language" href="http://en.wikipedia.org/wiki/Greek_language">Greek</a> <em>&pi;&rho;ώ&tau;&alpha;</em> (&quot;prota&quot;), meaning &quot;<em>of primary importance</em>&quot; and these molecules were first described and named by <a title="Jöns Jakob Berzelius" href="http://en.wikipedia.org/wiki/J%C3%B6ns_Jakob_Berzelius">J&ouml;ns Jakob Berzelius</a> in <a title="1838" href="http://en.wikipedia.org/wiki/1838">1838</a>. However, proteins' central role in living organisms was not fully appreciated until 1926, when <a title="James B. Sumner" href="http://en.wikipedia.org/wiki/James_B._Sumner">James B. Sumner</a> showed that the enzyme <a title="Urease" href="http://en.wikipedia.org/wiki/Urease">urease</a> was a protein.<sup class="reference" id="_ref-0"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-0">[1]</a></sup> The first protein to be sequenced was insulin, by <a title="Frederick Sanger" href="http://en.wikipedia.org/wiki/Frederick_Sanger">Frederick Sanger</a>, who won the Nobel Prize for this achievement in 1958. The first protein structures to be solved included <a title="Haemoglobin" href="http://en.wikipedia.org/wiki/Haemoglobin">haemoglobin</a> and <a title="Myoglobin" href="http://en.wikipedia.org/wiki/Myoglobin">myoglobin</a>, by <a title="Max Perutz" href="http://en.wikipedia.org/wiki/Max_Perutz">Max Perutz</a> and <a title="John Kendrew" href="http://en.wikipedia.org/wiki/John_Kendrew">Sir John Cowdery Kendrew</a>, respectively, in 1958.<sup class="reference" id="_ref-1"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-1">[2]</a></sup><sup class="reference" id="_ref-2"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-2">[3]</a></sup> Both proteins' three-dimensional structures were first determined by x-ray diffraction analysis; the structures of myoglobin and haemoglobin won the 1962 <a title="Nobel Prize in Chemistry" href="http://en.wikipedia.org/wiki/Nobel_Prize_in_Chemistry">Nobel Prize in Chemistry</a> for their discoverers.</p> 

<div class="noprint"><em>Main articles: <a title="Amino acid" href="http://en.wikipedia.org/wiki/Amino_acid">Amino acid</a> and <a title="Peptide bond" href="http://en.wikipedia.org/wiki/Peptide_bond">peptide bond</a></em></div>

<div class="thumbinner" style="WIDTH: 302px"><a class="internal" title="Resonance structures of the peptide bond that links individual amino acids to form a protein polymer." href="http://en.wikipedia.org/wiki/Image:Peptide_group_resonance.png"><img class="thumbimage" height="65" alt="Resonance structures of the peptide bond that links individual amino acids to form a protein polymer." width="300" longdesc="/wiki/Image:Peptide_group_resonance.png" src="http://upload.wikimedia.org/wikipedia/en/thumb/1/17/Peptide_group_resonance.png/300px-Peptide_group_resonance.png" /></a>

<div class="magnify" style="FLOAT: right"><a class="internal" title="Enlarge" href="http://en.wikipedia.org/wiki/Image:Peptide_group_resonance.png"><img height="11" alt="" width="15" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" /></a></div><a title="Resonance (chemistry)" href="http://en.wikipedia.org/wiki/Resonance_%28chemistry%29">Resonance</a> structures of the <a title="Peptide bond" href="http://en.wikipedia.org/wiki/Peptide_bond">peptide bond</a> that links individual amino acids to form a protein <a title="Polymer" href="http://en.wikipedia.org/wiki/Polymer">polymer</a>.</div>

<div class="thumbinner" style="WIDTH: 302px"><a class="internal" title="Section of a protein structure showing serine and alanine residues linked together by peptide bonds. Carbons are shown in white and hydrogens are omitted for clarity." href="http://en.wikipedia.org/wiki/Image:Peptide_bond.jpg"><img class="thumbimage" height="211" alt="Section of a protein structure showing serine and alanine residues linked together by peptide bonds. Carbons are shown in white and hydrogens are omitted for clarity." width="300" longdesc="/wiki/Image:Peptide_bond.jpg" src="http://upload.wikimedia.org/wikipedia/en/thumb/b/ba/Peptide_bond.jpg/300px-Peptide_bond.jpg" /></a>

<div class="magnify" style="FLOAT: right"><a class="internal" title="Enlarge" href="http://en.wikipedia.org/wiki/Image:Peptide_bond.jpg"><img height="11" alt="" width="15" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" /></a></div>

<p>Proteins are linear polymers built from 20 different L-&alpha;-<a title="Amino acid" href="http://en.wikipedia.org/wiki/Amino_acid">amino acids</a>. All amino acids share common structural features including an <a title="Alpha carbon" href="http://en.wikipedia.org/wiki/Alpha_carbon">&alpha; carbon</a> to which an <a title="Amino" href="http://en.wikipedia.org/wiki/Amino">amino</a> group, a <a title="Carboxyl" href="http://en.wikipedia.org/wiki/Carboxyl">carboxyl</a> group, and a variable <a title="Side chain" href="http://en.wikipedia.org/wiki/Side_chain">side chain</a> are <a title="Chemical bond" href="http://en.wikipedia.org/wiki/Chemical_bond">bonded</a>. 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.<sup class="reference" id="_ref-3"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-3">[4]</a></sup> The side chains of the standard amino acids, detailed in the <a title="List of standard amino acids" href="http://en.wikipedia.org/wiki/List_of_standard_amino_acids">list of standard amino acids</a>, have different chemical properties that produce proteins' three-dimensional structure and are therefore critical to protein function. The amino acids in a polypeptide chain are linked by <a title="Peptide bond" href="http://en.wikipedia.org/wiki/Peptide_bond">peptide bonds</a> formed in a <a title="Dehydration" href="http://en.wikipedia.org/wiki/Dehydration">dehydration</a> reaction. Once linked in the protein chain, an individual amino acid is called a <em>residue</em> and the linked series of carbon, nitrogen, and oxygen atoms are known as the <em>main chain</em> or <em>protein backbone</em>. The peptide bond has two <a title="Resonance (chemistry)" href="http://en.wikipedia.org/wiki/Resonance_%28chemistry%29">resonance</a> forms that contribute some <a title="Double bond" href="http://en.wikipedia.org/wiki/Double_bond">double bond</a> character and inhibit rotation around its axis, so that the alpha carbons are roughly <a title="Coplanar" href="http://en.wikipedia.org/wiki/Coplanar">coplanar</a>. The other two <a title="Dihedral angle" href="http://en.wikipedia.org/wiki/Dihedral_angle">dihedral angles</a> in the peptide bond determine the local shape assumed by the protein backbone.</p><p>Due to the chemical structure of the individual amino acids, the protein chain has directionality. The end of the protein with a free carboxyl group is known as the <a title="C-terminus" href="http://en.wikipedia.org/wiki/C-terminus">C-terminus</a> or carboxy terminus, while the end with a free amino group is known as the <a title="N-terminus" href="http://en.wikipedia.org/wiki/N-terminus">N-terminus</a> or amino terminus.</p><p>There is some ambiguity between the usage of the words <em>protein</em>, <em><a title="Polypeptide" href="http://en.wikipedia.org/wiki/Polypeptide">polypeptide</a></em>, and <em><a title="Peptide" href="http://en.wikipedia.org/wiki/Peptide">peptide</a></em>. <em>Protein</em> is generally used to refer to the complete biological molecule in a stable <a title="Tertiary structure" href="http://en.wikipedia.org/wiki/Tertiary_structure">conformation</a>, while <em>peptide</em> is generally reserved for a short amino acid oligomers often lacking a stable 3-dimensional structure. However, the boundary between the two is ill-defined and usually lies near 20-30 residues.<sup class="reference" id="_ref-Lodish_0"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-Lodish">[5]</a></sup> <em>Polypeptide</em> can refer to any single linear chain of amino acids, usually regardless of length, but often implies an absence of a single defined <a title="Tertiary structure" href="http://en.wikipedia.org/wiki/Tertiary_structure">conformation</a>.</p>

<div class="noprint"><em>Main article: <a title="Protein biosynthesis" href="http://en.wikipedia.org/wiki/Protein_biosynthesis">Protein biosynthesis</a></em></div>

<div class="floatleft"><span><a class="image" title="" href="http://en.wikipedia.org/wiki/Image:One_gene%2C_one_enzyme.gif"><img height="145" alt="" width="125" longdesc="/wiki/Image:One_gene%2C_one_enzyme.gif" src="http://upload.wikimedia.org/wikipedia/en/4/4e/One_gene%2C_one_enzyme.gif" /></a></span></div><p>Proteins are assembled from amino acids using information encoded in <a title="Gene" href="http://en.wikipedia.org/wiki/Gene">genes</a>. Each protein has its own unique amino acid sequence that is specified by the <a title="Nucleotide" href="http://en.wikipedia.org/wiki/Nucleotide">nucleotide</a> sequence of the gene encoding this protein. The <a title="Genetic code" href="http://en.wikipedia.org/wiki/Genetic_code">genetic code</a> is a set of three-nucleotide sets called <a title="Codon" href="http://en.wikipedia.org/wiki/Codon">codons</a> and each three-nucleotide combination stands for an amino acid, for example AUG stands for <a title="Methionine" href="http://en.wikipedia.org/wiki/Methionine">methionine</a>. Because <a title="DNA" href="http://en.wikipedia.org/wiki/DNA">DNA</a> contains four nucleotides, the total number of possible codons is 64; hence, there is some redundancy in the genetic code and some amino acids are specified by more than one codon. Genes encoded in DNA are first <a title="Transcription (genetics)" href="http://en.wikipedia.org/wiki/Transcription_%28genetics%29">transcribed</a> into pre-<a title="Messenger RNA" href="http://en.wikipedia.org/wiki/Messenger_RNA">messenger RNA</a> (mRNA) by proteins such as <a title="RNA polymerase" href="http://en.wikipedia.org/wiki/RNA_polymerase">RNA polymerase</a>. Most organisms then process the pre-mRNA (also known as a <em>primary transcript</em>) using various forms of <a title="Post-transcriptional modification" href="http://en.wikipedia.org/wiki/Post-transcriptional_modification">post-transcriptional modification</a> to form the mature mRNA, which is then used as a template for protein synthesis by the <a title="Ribosome" href="http://en.wikipedia.org/wiki/Ribosome">ribosome</a>. In <a title="Prokaryote" href="http://en.wikipedia.org/wiki/Prokaryote">prokaryotes</a> the mRNA may either be used as soon as it is produced, or be bound by a ribosome after having moved away from the <a title="Nucleoid" href="http://en.wikipedia.org/wiki/Nucleoid">nucleoid</a>. In contrast, <a title="Eukaryote" href="http://en.wikipedia.org/wiki/Eukaryote">eukaryotes</a> make mRNA in the <a title="Cell nucleus" href="http://en.wikipedia.org/wiki/Cell_nucleus">cell nucleus</a> and then translocate it across the <a title="Nuclear membrane" href="http://en.wikipedia.org/wiki/Nuclear_membrane">nuclear membrane</a> into the <a title="Cytoplasm" href="http://en.wikipedia.org/wiki/Cytoplasm">cytoplasm</a>, where <a title="Protein biosynthesis" href="http://en.wikipedia.org/wiki/Protein_biosynthesis">protein synthesis</a> then takes place. The rate of protein synthesis is higher in prokaryotes than eukaryotes and can reach up to 20 amino acids per second.<sup class="reference" id="_ref-Dobson_0"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-Dobson">[6]</a></sup></p><p>The process of synthesizing a protein from an mRNA template is known as <a title="Translation (genetics)" href="http://en.wikipedia.org/wiki/Translation_%28genetics%29">translation</a>. The mRNA is loaded onto the ribosome and is read three nucleotides at a time by matching each codon to its <a title="Base pair" href="http://en.wikipedia.org/wiki/Base_pair">base pairing</a> <a title="Anticodon" href="http://en.wikipedia.org/wiki/Anticodon">anticodon</a> located on a <a title="Transfer RNA" href="http://en.wikipedia.org/wiki/Transfer_RNA">transfer RNA</a> molecule, which carries the amino acid corresponding to the codon it recognizes. The enzyme <a title="Aminoacyl tRNA synthetase" href="http://en.wikipedia.org/wiki/Aminoacyl_tRNA_synthetase">aminoacyl tRNA synthetase</a> &quot;charges&quot; the tRNA molecules with the correct amino acids. The growing polypeptide is often termed the <em>nascent chain</em>. Proteins are always biosynthesized from N-terminus to C-terminus.</p><p>The size of a synthesized protein can be measured by the number of amino acids it contains and by its total <a title="Molecular mass" href="http://en.wikipedia.org/wiki/Molecular_mass">molecular mass</a>, which is normally reported in units of <em>daltons</em> (synonymous with <a title="Atomic mass unit" href="http://en.wikipedia.org/wiki/Atomic_mass_unit">atomic mass units</a>), or the derivative unit kilodalton (kDa). <a title="Yeast" href="http://en.wikipedia.org/wiki/Yeast">Yeast</a> proteins are on average 466 amino acids long and 53 kDa in mass.<sup class="reference" id="_ref-Lodish_1"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-Lodish">[5]</a></sup> The largest known proteins are the <a title="Titin" href="http://en.wikipedia.org/wiki/Titin">titins</a>, a component of the <a title="Muscle" href="http://en.wikipedia.org/wiki/Muscle">muscle</a> <a title="Sarcomere" href="http://en.wikipedia.org/wiki/Sarcomere">sarcomere</a>, with a molecular mass of almost 3,000 kDa and a total length of almost 27,000 amino acids.<sup class="reference" id="_ref-4"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-4">[7]</a></sup></p>

<p>Short proteins can also be synthesized chemically by a family of methods known as <a title="Peptide synthesis" href="http://en.wikipedia.org/wiki/Peptide_synthesis">peptide synthesis</a>, which rely on <a title="Organic synthesis" href="http://en.wikipedia.org/wiki/Organic_synthesis">organic synthesis</a> techniques such as <a title="Chemical ligation" href="http://en.wikipedia.org/wiki/Chemical_ligation">chemical ligation</a> to produce peptides in high yield.<sup class="reference" id="_ref-5"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-5">[8]</a></sup> Chemical synthesis allows for the introduction of non-natural amino acids into polypeptide chains, such as attachment of <a title="Fluorescent" href="http://en.wikipedia.org/wiki/Fluorescent">fluorescent</a> probes to amino acid side chains.<sup class="reference" id="_ref-6"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-6">[9]</a></sup> These methods are useful in laboratory <a title="Biochemistry" href="http://en.wikipedia.org/wiki/Biochemistry">biochemistry</a> and <a title="Cell biology" href="http://en.wikipedia.org/wiki/Cell_biology">cell biology</a>, 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 <a title="Tertiary structure" href="http://en.wikipedia.org/wiki/Tertiary_structure">tertiary structure</a>. Most chemical synthesis methods proceed from C-terminus to N-terminus, opposite the biological reaction.</p>

<div class="noprint"><em>Main article: <a title="Protein structure" href="http://en.wikipedia.org/wiki/Protein_structure">Protein structure</a></em></div>

<div class="thumbinner" style="WIDTH: 502px"><a class="internal" title="Three possible representations of the three-dimensional structure of the protein triose phosphate isomerase. Left: all-atom representation colored by atom type. Middle: simplified representation illustrating the backbone conformation, colored by secondary structure. Right: Solvent-accessible surface representation colored by residue type (acidic residues red, basic residues blue, polar residues green, nonpolar residues white)." href="http://en.wikipedia.org/wiki/Image:Proteinviews-1tim.png"><img class="thumbimage" height="200" alt="Three possible representations of the three-dimensional structure of the protein triose phosphate isomerase. Left: all-atom representation colored by atom type. Middle: simplified representation illustrating the backbone conformation, colored by secondary structure. Right: Solvent-accessible surface representation colored by residue type (acidic residues red, basic residues blue, polar residues green, nonpolar residues white)." width="500" longdesc="/wiki/Image:Proteinviews-1tim.png" src="http://upload.wikimedia.org/wikipedia/commons/thumb/6/6e/Proteinviews-1tim.png/500px-Proteinviews-1tim.png" /></a>

<div class="magnify" style="FLOAT: right"><a class="internal" title="Enlarge" href="http://en.wikipedia.org/wiki/Image:Proteinviews-1tim.png"><img height="11" alt="" width="15" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" /></a></div>Three possible representations of the three-dimensional structure of the protein <a title="Triose phosphate isomerase" href="http://en.wikipedia.org/wiki/Triose_phosphate_isomerase">triose phosphate isomerase</a>. Left: all-atom representation colored by atom type. Middle: simplified representation illustrating the backbone conformation, colored by secondary structure. Right: Solvent-accessible surface representation colored by residue type (acidic residues red, basic residues blue, polar residues green, nonpolar residues white).</div>

<p>Most proteins <a title="Protein folding" href="http://en.wikipedia.org/wiki/Protein_folding">fold</a> into unique 3-dimensional structures. The shape into which a protein naturally folds is known as its <a title="Native state" href="http://en.wikipedia.org/wiki/Native_state">native state</a>. Although many proteins can fold unassisted simply through the structural propensities of their component amino acids, others require the aid of molecular <a title="Chaperone" href="http://en.wikipedia.org/wiki/Chaperone">chaperones</a> to efficiently fold to their native states. Biochemists often refer to four distinct aspects of a protein's structure:</p>

<li><em><a title="Primary structure" href="http://en.wikipedia.org/wiki/Primary_structure">Primary structure</a></em>: the <a title="Peptide sequence" href="http://en.wikipedia.org/wiki/Peptide_sequence">amino acid sequence</a> </li> <li><em><a title="Secondary structure" href="http://en.wikipedia.org/wiki/Secondary_structure">Secondary structure</a></em>: regularly repeating local structures stabilized by <a title="Hydrogen bond" href="http://en.wikipedia.org/wiki/Hydrogen_bond">hydrogen bonds</a>. The most common examples are the <a title="Alpha helix" href="http://en.wikipedia.org/wiki/Alpha_helix">alpha helix</a> and <a title="Beta sheet" href="http://en.wikipedia.org/wiki/Beta_sheet">beta sheet</a>.<sup class="reference" id="_ref-Branden_0"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-Branden">[10]</a></sup> Because secondary structures are local, many regions of different secondary structure can be present in the same protein molecule. </li> <li><em><a title="Tertiary structure" href="http://en.wikipedia.org/wiki/Tertiary_structure">Tertiary structure</a></em>: 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 <a title="Hydrophobic core" href="http://en.wikipedia.org/wiki/Hydrophobic_core">hydrophobic core</a>, but also through <a title="Salt bridge (protein)" href="http://en.wikipedia.org/wiki/Salt_bridge_%28protein%29">salt bridges</a>, hydrogen bonds, <a title="Disulfide bond" href="http://en.wikipedia.org/wiki/Disulfide_bond">disulfide bonds</a>, and even <a title="Post-translational modification" href="http://en.wikipedia.org/wiki/Post-translational_modification">post-translational modifications</a>. The term &quot;tertiary structure&quot; is often used as synonymous with the term <em>fold</em>. </li> <li><em><a title="Quaternary structure" href="http://en.wikipedia.org/wiki/Quaternary_structure">Quaternary structure</a></em>: the shape or structure that results from the <a title="Protein-protein interaction" href="http://en.wikipedia.org/wiki/Protein-protein_interaction">interaction</a> of more than one protein molecule, usually called <em><a title="Protein subunit" href="http://en.wikipedia.org/wiki/Protein_subunit">protein subunits</a></em> in this context, which function as part of the larger assembly or <a title="Protein complex" href="http://en.wikipedia.org/wiki/Protein_complex">protein complex</a>. </li>

<div class="thumbinner" style="WIDTH: 152px"><a class="internal" title="NMR structures of the protein cytochrome c in solution show the constantly shifting dynamic structure of the protein. Larger version." href="http://en.wikipedia.org/wiki/Image:Protein_Dynamics_Cytochrome_C_2NEW_smaller.gif"><img class="thumbimage" height="122" alt="NMR structures of the protein cytochrome c in solution show the constantly shifting dynamic structure of the protein. Larger version." width="150" longdesc="/wiki/Image:Protein_Dynamics_Cytochrome_C_2NEW_smaller.gif" src="http://upload.wikimedia.org/wikipedia/en/a/ae/Protein_Dynamics_Cytochrome_C_2NEW_smaller.gif" /></a>

<div class="magnify" style="FLOAT: right"><a class="internal" title="Enlarge" href="http://en.wikipedia.org/wiki/Image:Protein_Dynamics_Cytochrome_C_2NEW_smaller.gif"><img height="11" alt="" width="15" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" /></a></div>NMR structures of the protein <a title="Cytochrome c" href="http://en.wikipedia.org/wiki/Cytochrome_c">cytochrome c</a> in solution show the constantly shifting dynamic structure of the protein. <a title="Image:Protein Dynamics Cytochrome C 2NEW small.gif" href="http://en.wikipedia.org/wiki/Image:Protein_Dynamics_Cytochrome_C_2NEW_small.gif">Larger version</a>.</div>

<p>Proteins are not entirely rigid molecules. In addition to these levels of structure, proteins may shift between several related structures in performing their biological function. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as &quot;<a title="Chemical conformation" href="http://en.wikipedia.org/wiki/Chemical_conformation">conformations</a>,&quot; and transitions between them are called <em>conformational changes.</em> Such changes are often induced by the binding of a <a title="Substrate (biochemistry)" href="http://en.wikipedia.org/wiki/Substrate_%28biochemistry%29">substrate</a> molecule to an enzyme's <a title="Active site" href="http://en.wikipedia.org/wiki/Active_site">active site</a>, or the physical region of the protein that participates in chemical catalysis. In solution all proteins also undergo variation in structure through thermal vibration and the collision with other molecules, see the animation on the right.</p>

<div class="thumbinner" style="WIDTH: 502px"><a class="internal" title="Molecular surface of several proteins showing their comparative sizes. From left to right are: Antibody (IgG), Hemoglobin, Insulin (a hormone), Adenylate kinase (an enzyme), and Glutamine synthetase (an enzyme)." href="http://en.wikipedia.org/wiki/Image:Protein_Composite.jpg"><img class="thumbimage" height="144" alt="Molecular surface of several proteins showing their comparative sizes. From left to right are: Antibody (IgG), Hemoglobin, Insulin (a hormone), Adenylate kinase (an enzyme), and Glutamine synthetase (an enzyme)." width="500" longdesc="/wiki/Image:Protein_Composite.jpg" src="http://upload.wikimedia.org/wikipedia/commons/thumb/5/53/Protein_Composite.jpg/500px-Protein_Composite.jpg" /></a>

<div class="magnify" style="FLOAT: right"><a class="internal" title="Enlarge" href="http://en.wikipedia.org/wiki/Image:Protein_Composite.jpg"><img height="11" alt="" width="15" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" /></a></div>Molecular surface of several proteins showing their comparative sizes. From left to right are: <a title="Antibody" href="http://en.wikipedia.org/wiki/Antibody">Antibody</a> (IgG), <a title="Hemoglobin" href="http://en.wikipedia.org/wiki/Hemoglobin">Hemoglobin</a>, <a title="Insulin" href="http://en.wikipedia.org/wiki/Insulin">Insulin</a> (a hormone), <a title="Adenylate kinase" href="http://en.wikipedia.org/wiki/Adenylate_kinase">Adenylate kinase</a> (an enzyme), and <a title="Glutamine synthetase" href="http://en.wikipedia.org/wiki/Glutamine_synthetase">Glutamine synthetase</a> (an enzyme).</div>

<p>Proteins can be informally divided into three main classes, which correlate with typical tertiary structures: <a title="Globular protein" href="http://en.wikipedia.org/wiki/Globular_protein">globular proteins</a>, <a title="Fibrous protein" href="http://en.wikipedia.org/wiki/Fibrous_protein">fibrous proteins</a>, and <a title="Membrane protein" href="http://en.wikipedia.org/wiki/Membrane_protein">membrane proteins</a>. Almost all globular proteins are <a title="Soluble" href="http://en.wikipedia.org/wiki/Soluble">soluble</a> and many are enzymes. Fibrous proteins are often structural; membrane proteins often serve as <a title="Receptor (biochemistry)" href="http://en.wikipedia.org/wiki/Receptor_%28biochemistry%29">receptors</a> or provide channels for polar or charged molecules to pass through the cell membrane.</p><p>A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own <a title="Dehydration" href="http://en.wikipedia.org/wiki/Dehydration">dehydration</a>, are called <a title="Dehydron" href="http://en.wikipedia.org/wiki/Dehydron">dehydrons</a>.</p>

<p>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 <a title="X-ray crystallography" href="http://en.wikipedia.org/wiki/X-ray_crystallography">X-ray crystallography</a> and <a title="Protein NMR" href="http://en.wikipedia.org/wiki/Protein_NMR">NMR spectroscopy</a>, both of which can produce information at <a title="Atom" href="http://en.wikipedia.org/wiki/Atom">atomic</a> resolution. <a title="Cryoelectron microscopy" href="http://en.wikipedia.org/wiki/Cryoelectron_microscopy">Cryoelectron microscopy</a> is used to produce lower-resolution structural information about very large protein complexes, including assembled <a title="Virus" href="http://en.wikipedia.org/wiki/Virus">viruses</a>;<sup class="reference" id="_ref-Branden_1"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-Branden">[10]</a></sup> a variant known as <a title="Electron crystallography" href="http://en.wikipedia.org/wiki/Electron_crystallography">electron crystallography</a> can also produce high-resolution information in some cases, especially for two-dimensional crystals of membrane proteins.<sup class="reference" id="_ref-7"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-7">[11]</a></sup> Solved structures are usually deposited in the <a title="Protein Data Bank" href="http://en.wikipedia.org/wiki/Protein_Data_Bank">Protein Data Bank</a> (PDB), a freely available resource from which structural data about thousands of proteins can be obtained in the form of <a title="Cartesian coordinates" href="http://en.wikipedia.org/wiki/Cartesian_coordinates">Cartesian coordinates</a> for each atom in the protein.</p><p>There are many more known gene sequences than there are solved protein structures. Further, the set of solved structures is biased toward those proteins that can be easily subjected to the experimental conditions required by one of the major structure determination methods. In particular, globular proteins are comparatively easy to <a title="Crystallize" href="http://en.wikipedia.org/wiki/Crystallize">crystallize</a> in preparation for X-ray crystallography, which remains the oldest and most common structure determination technique. Membrane proteins, by contrast, are difficult to crystallize and are underrepresented in the PDB.<sup class="reference" id="_ref-8"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-8">[12]</a></sup> <a title="Structural genomics" href="http://en.wikipedia.org/wiki/Structural_genomics">Structural genomics</a> initiatives have attempted to remedy these deficiencies by systematically solving representative structures of major fold classes. <a title="Protein structure prediction" href="http://en.wikipedia.org/wiki/Protein_structure_prediction">Protein structure prediction</a> methods attempt to provide a means of generating a plausible structure for proteins whose structures have not been experimentally determined.</p>

<p>Proteins are the chief actors within the cell, said to be carrying out the duties specified by the information encoded in genes.<sup class="reference" id="_ref-Lodish_2"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-Lodish">[5]</a></sup> With the exception of certain types of <a title="RNA" href="http://en.wikipedia.org/wiki/RNA">RNA</a>, most other biological molecules are relatively inert elements upon which proteins act. Proteins make up half the dry weight of an <em><a title="Escherichia coli" href="http://en.wikipedia.org/wiki/Escherichia_coli">Escherichia coli</a></em> cell, while other macromolecules such as DNA and RNA make up only 3% and 20% respectively.<sup class="reference" id="_ref-Voet_0"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-Voet">[13]</a></sup> The set of proteins expressed in a particular cell or cell type is known as its <a title="Proteome" href="http://en.wikipedia.org/wiki/Proteome">proteome</a>.</p>

<div class="thumbinner" style="WIDTH: 352px"><a class="internal" title="The enzyme hexokinase is shown as a simple ball-and-stick molecular model. To scale in the top right-hand corner are its two substrates, ATP and glucose." href="http://en.wikipedia.org/wiki/Image:Hexokinase_ball_and_stick_model%2C_with_substrates_to_scale_copy.png"><img class="thumbimage" height="250" alt="The enzyme hexokinase is shown as a simple ball-and-stick molecular model. To scale in the top right-hand corner are its two substrates, ATP and glucose." width="350" longdesc="/wiki/Image:Hexokinase_ball_and_stick_model%2C_with_substrates_to_scale_copy.png" src="http://upload.wikimedia.org/wikipedia/en/thumb/e/e7/Hexokinase_ball_and_stick_model%2C_with_substrates_to_scale_copy.png/350px-Hexokinase_ball_and_stick_model%2C_with_substrates_to_scale_copy.png" /></a>

<div class="magnify" style="FLOAT: right"><a class="internal" title="Enlarge" href="http://en.wikipedia.org/wiki/Image:Hexokinase_ball_and_stick_model%2C_with_substrates_to_scale_copy.png"><img height="11" alt="" width="15" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" /></a></div>The enzyme <a title="Hexokinase" href="http://en.wikipedia.org/wiki/Hexokinase">hexokinase</a> is shown as a simple ball-and-stick molecular model. To scale in the top right-hand corner are its two substrates, <a title="Adenosine triphosphate" href="http://en.wikipedia.org/wiki/Adenosine_triphosphate">ATP</a> and <a title="Glucose" href="http://en.wikipedia.org/wiki/Glucose">glucose</a>.</div>

<p>The chief characteristic of proteins that enables them to carry out their diverse cellular 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 <a title="Binding site" href="http://en.wikipedia.org/wiki/Binding_site">binding site</a> and is often a depression or &quot;pocket&quot; 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 <a title="Ribonuclease inhibitor" href="http://en.wikipedia.org/wiki/Ribonuclease_inhibitor">ribonuclease inhibitor</a> protein binds to human <a title="Angiogenin" href="http://en.wikipedia.org/wiki/Angiogenin">angiogenin</a> with a sub-femtomolar <a title="Dissociation constant" href="http://en.wikipedia.org/wiki/Dissociation_constant">dissociation constant</a> (&lt;10^-15 M) but does not bind at all to its amphibian homolog <a title="Onconase" href="http://en.wikipedia.org/wiki/Onconase">onconase</a> (&gt;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 <a title="Aminoacyl tRNA synthetase" href="http://en.wikipedia.org/wiki/Aminoacyl_tRNA_synthetase">aminoacyl tRNA synthetase</a> specific to the amino acid <a title="Valine" href="http://en.wikipedia.org/wiki/Valine">valine</a> discriminates against the very similar side chain of the amino acid <a title="Isoleucine" href="http://en.wikipedia.org/wiki/Isoleucine">isoleucine</a>.</p><p>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 <a title="Oligomer" href="http://en.wikipedia.org/wiki/Oligomer">oligomerize</a> to form fibrils; this process occurs often in structural proteins that consist of globular monomers that self-associate to form rigid fibers. <a title="Protein-protein interaction" href="http://en.wikipedia.org/wiki/Protein-protein_interaction">Protein-protein interactions</a> also regulate enzymatic activity, control progression through the <a title="Cell cycle" href="http://en.wikipedia.org/wiki/Cell_cycle">cell cycle</a>, and allow the assembly of large <a title="Protein complex" href="http://en.wikipedia.org/wiki/Protein_complex">protein complexes</a> 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 <a title="Cell signaling" href="http://en.wikipedia.org/wiki/Cell_signaling">signaling</a> networks.</p>

<div class="noprint"><em>Main article: <a title="Enzyme" href="http://en.wikipedia.org/wiki/Enzyme">Enzyme</a></em></div>

<p>The best-known role of proteins in the cell is their duty as <a title="Enzyme" href="http://en.wikipedia.org/wiki/Enzyme">enzymes</a>, which <a title="Catalysis" href="http://en.wikipedia.org/wiki/Catalysis">catalyze</a> chemical reactions. Enzymes are usually highly specific catalysts that accelerate only one or a few chemical reactions. Enzymes effect most of the reactions involved in <a title="Metabolism" href="http://en.wikipedia.org/wiki/Metabolism">metabolism</a> and <a title="Catabolism" href="http://en.wikipedia.org/wiki/Catabolism">catabolism</a> as well as <a title="DNA replication" href="http://en.wikipedia.org/wiki/DNA_replication">DNA replication</a>, <a title="DNA repair" href="http://en.wikipedia.org/wiki/DNA_repair">DNA repair</a>, and <a title="RNA synthesis" href="http://en.wikipedia.org/wiki/RNA_synthesis">RNA synthesis</a>. Some enzymes act on other proteins to add or remove chemical groups in a process known as <a title="Post-translational modification" href="http://en.wikipedia.org/wiki/Post-translational_modification">post-translational modification</a>. About 4,000 reactions are known to be catalyzed by enzymes.<sup class="reference" id="_ref-9"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-9">[14]</a></sup> The rate acceleration conferred by enzymatic catalysis is often enormous - as much as 10¹⁷-fold increase in rate over the uncatalyzed reaction in the case of <a title="Orotate decarboxylase" href="http://en.wikipedia.org/wiki/Orotate_decarboxylase">orotate decarboxylase</a> (78 million years without the enzyme, 18 milliseconds with the enzyme).<sup class="reference" id="_ref-10"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-10">[15]</a></sup></p><p>The molecules bound and acted upon by enzymes are known as <a title="Substrate (biochemistry)" href="http://en.wikipedia.org/wiki/Substrate_%28biochemistry%29">substrates</a>. 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 - 3-4 residues on average - that are directly involved in catalysis.<sup class="reference" id="_ref-11"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-11">[16]</a></sup> The region of the enzyme that binds the substrate and contains the catalytic residues is known as the <a title="Active site" href="http://en.wikipedia.org/wiki/Active_site">active site</a>.</p>

<div class="thumbinner" style="WIDTH: 152px"><a class="internal" title="A mouse antibody against cholera that binds a carbohydrate antigen." href="http://en.wikipedia.org/wiki/Image:Mouse-cholera-antibody-1f4x.png"><img class="thumbimage" height="224" alt="A mouse antibody against cholera that binds a carbohydrate antigen." width="150" longdesc="/wiki/Image:Mouse-cholera-antibody-1f4x.png" src="http://upload.wikimedia.org/wikipedia/commons/thumb/3/3b/Mouse-cholera-antibody-1f4x.png/150px-Mouse-cholera-antibody-1f4x.png" /></a>

<div class="magnify" style="FLOAT: right"><a class="internal" title="Enlarge" href="http://en.wikipedia.org/wiki/Image:Mouse-cholera-antibody-1f4x.png"><img height="11" alt="" width="15" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" /></a></div>A <a title="Mouse" href="http://en.wikipedia.org/wiki/Mouse">mouse</a> antibody against <a title="Cholera" href="http://en.wikipedia.org/wiki/Cholera">cholera</a> that binds a <a title="Carbohydrate" href="http://en.wikipedia.org/wiki/Carbohydrate">carbohydrate</a> antigen.</div>

<p>Many proteins are involved in the process of <a title="Cell signaling" href="http://en.wikipedia.org/wiki/Cell_signaling">cell signaling</a> and <a title="Signal transduction" href="http://en.wikipedia.org/wiki/Signal_transduction">signal transduction</a>. Some proteins, such as <a title="Insulin" href="http://en.wikipedia.org/wiki/Insulin">insulin</a>, are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant <a title="Biological tissue" href="http://en.wikipedia.org/wiki/Biological_tissue">tissues</a>. Others are <a title="Membrane protein" href="http://en.wikipedia.org/wiki/Membrane_protein">membrane proteins</a> that act as <a title="Receptor (biochemistry)" href="http://en.wikipedia.org/wiki/Receptor_%28biochemistry%29">receptors</a> 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 <a title="Conformational change" href="http://en.wikipedia.org/wiki/Conformational_change">conformational change</a> detected by other proteins within the cell.</p><p><a title="Antibodies" href="http://en.wikipedia.org/wiki/Antibodies">Antibodies</a> are protein components of <a title="Adaptive immune system" href="http://en.wikipedia.org/wiki/Adaptive_immune_system">adaptive immune system</a> whose main function is to bind <a title="Antigen" href="http://en.wikipedia.org/wiki/Antigen">antigens</a>, or foreign substances in the body, and target them for destruction. Antibodies can be <a title="Secrete" href="http://en.wikipedia.org/wiki/Secrete">secreted</a> into the extracellular environment or anchored in the membranes of specialized <a title="B cell" href="http://en.wikipedia.org/wiki/B_cell">B cells</a> known as <a title="Plasma cell" href="http://en.wikipedia.org/wiki/Plasma_cell">plasma cells</a>. While 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.</p><p>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 <a title="Ligand" href="http://en.wikipedia.org/wiki/Ligand">ligand</a> 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 <a title="Haemoglobin" href="http://en.wikipedia.org/wiki/Haemoglobin">haemoglobin</a>, which transports <a title="Oxygen" href="http://en.wikipedia.org/wiki/Oxygen">oxygen</a> from the <a title="Lung" href="http://en.wikipedia.org/wiki/Lung">lungs</a> to other organs and tissues in all <a title="Vertebrate" href="http://en.wikipedia.org/wiki/Vertebrate">vertebrates</a> and has close <a title="Homolog" href="http://en.wikipedia.org/wiki/Homolog">homologs</a> in every biological <a title="Kingdom (biology)" href="http://en.wikipedia.org/wiki/Kingdom_%28biology%29">kingdom</a>.</p><p><a title="Transmembrane protein" href="http://en.wikipedia.org/wiki/Transmembrane_protein">Transmembrane proteins</a> can also serve as ligand transport proteins that alter the <a title="Permeability" href="http://en.wikipedia.org/wiki/Permeability">permeability</a> of the cell's membrane to small molecules and ions. The membrane alone has a <a title="Hydrophobic" href="http://en.wikipedia.org/wiki/Hydrophobic">hydrophobic</a> core through which <a title="Polar" href="http://en.wikipedia.org/wiki/Polar">polar</a> or charged molecules cannot <a title="Diffusion" href="http://en.wikipedia.org/wiki/Diffusion">diffuse</a>. Membrane proteins contain internal channels that allow such molecules to enter and exit the cell. Many <a title="Ion channel" href="http://en.wikipedia.org/wiki/Ion_channel">ion channel</a> proteins are specialized to select for only a particular ion; for example, <a title="Potassium" href="http://en.wikipedia.org/wiki/Potassium">potassium</a> and <a title="Sodium" href="http://en.wikipedia.org/wiki/Sodium">sodium</a> channels often discriminate for only one of the two ions.</p>

<p>Structural proteins confer stiffness and rigidity to otherwise fluid biological components. Most structural proteins are <a title="Fibrous protein" href="http://en.wikipedia.org/wiki/Fibrous_protein">fibrous proteins</a>; for example, <a title="Actin" href="http://en.wikipedia.org/wiki/Actin">actin</a> and <a title="Tubulin" href="http://en.wikipedia.org/wiki/Tubulin">tubulin</a> are globular and soluble as monomers but <a title="Polymer" href="http://en.wikipedia.org/wiki/Polymer">polymerize</a> to form long, stiff fibers that comprise the <a title="Cytoskeleton" href="http://en.wikipedia.org/wiki/Cytoskeleton">cytoskeleton</a>, which allows the cell to maintain its shape and size. <a title="Collagen" href="http://en.wikipedia.org/wiki/Collagen">Collagen</a> and <a title="Elastin" href="http://en.wikipedia.org/wiki/Elastin">elastin</a> are critical components of <a title="Connective tissue" href="http://en.wikipedia.org/wiki/Connective_tissue">connective tissue</a> such as <a title="Cartilage" href="http://en.wikipedia.org/wiki/Cartilage">cartilage</a>, and <a title="Keratin" href="http://en.wikipedia.org/wiki/Keratin">keratin</a> is found in hard or filamentous structures such as <a title="Hair" href="http://en.wikipedia.org/wiki/Hair">hair</a>, <a title="Nail (anatomy)" href="http://en.wikipedia.org/wiki/Nail_%28anatomy%29">nails</a>, <a title="Feather" href="http://en.wikipedia.org/wiki/Feather">feathers</a>, <a title="Hoof" href="http://en.wikipedia.org/wiki/Hoof">hooves</a>, and some <a title="Animal shell" href="http://en.wikipedia.org/wiki/Animal_shell">animal shells</a>.</p><p>Other proteins that serve structural functions are <a title="Motor protein" href="http://en.wikipedia.org/wiki/Motor_protein">motor proteins</a> such as <a title="Myosin" href="http://en.wikipedia.org/wiki/Myosin">myosin</a>, <a title="Kinesin" href="http://en.wikipedia.org/wiki/Kinesin">kinesin</a>, and <a title="Dynein" href="http://en.wikipedia.org/wiki/Dynein">dynein</a>, which are capable of generating mechanical forces. These proteins are crucial for cellular <a title="Motility" href="http://en.wikipedia.org/wiki/Motility">motility</a> of single-celled organisms and the <a title="Spermatozoon" href="http://en.wikipedia.org/wiki/Spermatozoon">sperm</a> of many sexually reproducing multicellular organisms. They also generate the forces exerted by contracting <a title="Muscle" href="http://en.wikipedia.org/wiki/Muscle">muscles</a>.</p>

<div class="noprint"><em>Main article: <a title="Protein methods" href="http://en.wikipedia.org/wiki/Protein_methods">Protein methods</a></em></div>

<p>As some of the most commonly studied biological molecules, the activities and structures of proteins are examined both <em>in vitro</em> and <em>in vivo</em>. <em>In vitro</em> studies of purified proteins in controlled environments are useful for learning how a protein carries out its function: for example, <a title="Enzyme kinetics" href="http://en.wikipedia.org/wiki/Enzyme_kinetics">enzyme kinetics</a> studies explore the <a title="Reaction mechanism" href="http://en.wikipedia.org/wiki/Reaction_mechanism">chemical mechanism</a> of an enzyme's catalytic activity and its relative affinity for various possible substrate molecules. By contrast, <em>in vivo</em> experiments on proteins' activities within cells or even within whole organisms can provide complementary information about where a protein functions and how it is regulated.</p>

<div class="noprint"><em>Main article: <a title="Protein purification" href="http://en.wikipedia.org/wiki/Protein_purification">Protein purification</a></em></div>

<p>In order to perform <em>in vitro</em> analyses, a protein must be purified away from other cellular components. This process usually begins with <a title="Cytolysis" href="http://en.wikipedia.org/wiki/Cytolysis">cell lysis</a>, in which a cell's membrane is disrupted and its internal contents released into a solution known as a <a title="Crude lysate" href="http://en.wikipedia.org/wiki/Crude_lysate">crude lysate</a>. The resulting mixture can be purified using <a title="Ultracentrifugation" href="http://en.wikipedia.org/wiki/Ultracentrifugation">ultracentrifugation</a>, which fractionates the various cellular components into fractions containing soluble proteins; membrane <a title="Lipid" href="http://en.wikipedia.org/wiki/Lipid">lipids</a> and proteins; cellular <a title="Organelle" href="http://en.wikipedia.org/wiki/Organelle">organelles</a>, and <a title="Nucleic acid" href="http://en.wikipedia.org/wiki/Nucleic_acid">nucleic acids</a>. <a title="Precipitation" href="http://en.wikipedia.org/wiki/Precipitation">Precipitation</a> by a method known as <a title="Salting out" href="http://en.wikipedia.org/wiki/Salting_out">salting out</a> can concentrate the proteins from this lysate. Various types of <a title="Chromatography" href="http://en.wikipedia.org/wiki/Chromatography">chromatography</a> 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 <a title="Gel electrophoresis" href="http://en.wikipedia.org/wiki/Gel_electrophoresis">gel electrophoresis</a> if the desired protein's molecular weight is known, by <a title="Spectroscopy" href="http://en.wikipedia.org/wiki/Spectroscopy">spectroscopy</a> if the protein has distinguishable spectroscopic features, or by <a title="Enzyme assay" href="http://en.wikipedia.org/wiki/Enzyme_assay">enzyme assays</a> if the protein has enzymatic activity.</p><p>For natural proteins, a series of purification steps may be necessary to obtain protein sufficiently pure for laboratory applications. To simplify this process, <a title="Genetic engineering" href="http://en.wikipedia.org/wiki/Genetic_engineering">genetic engineering</a> is often used to add chemical features to proteins that make them easier to purify without affecting their structure or activity. Here, a &quot;tag&quot; consisting of a specific amino acid sequence, often a series of <a title="Histidine" href="http://en.wikipedia.org/wiki/Histidine">histidine</a> residues (a &quot;<a title="His-tag" href="http://en.wikipedia.org/wiki/His-tag">His-tag</a>&quot;), is attached to one terminus of the protein. As a result, when the lysate is passed over a chromatography column containing <a title="Nickel" href="http://en.wikipedia.org/wiki/Nickel">nickel</a>, the histidine residues ligate the nickel and attach to the column while the untagged components of the lysate pass unimpeded.</p>

<div class="thumbinner" style="WIDTH: 302px"><a class="internal" title="Proteins in different cellular compartments and structures tagged with green fluorescent protein (here, white)." href="http://en.wikipedia.org/wiki/Image:Localisations02eng.jpg"><img class="thumbimage" height="395" alt="Proteins in different cellular compartments and structures tagged with green fluorescent protein (here, white)." width="300" longdesc="/wiki/Image:Localisations02eng.jpg" src="http://upload.wikimedia.org/wikipedia/commons/thumb/6/6e/Localisations02eng.jpg/300px-Localisations02eng.jpg" /></a>

<div class="magnify" style="FLOAT: right"><a class="internal" title="Enlarge" href="http://en.wikipedia.org/wiki/Image:Localisations02eng.jpg"><img height="11" alt="" width="15" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" /></a></div>Proteins in different <a title="Cellular compartment" href="http://en.wikipedia.org/wiki/Cellular_compartment">cellular compartments</a> and structures tagged with <a title="Green fluorescent protein" href="http://en.wikipedia.org/wiki/Green_fluorescent_protein">green fluorescent protein</a> (here, white).</div>

<p>The study of proteins <em>in vivo</em> is often concerned with the synthesis and localization of the protein within the cell. Although many intracellular proteins are synthesized in the <a title="Cytoplasm" href="http://en.wikipedia.org/wiki/Cytoplasm">cytoplasm</a> and membrane-bound or secreted proteins in the <a title="Endoplasmic reticulum" href="http://en.wikipedia.org/wiki/Endoplasmic_reticulum">endoplasmic reticulum</a>, the specifics of how proteins are <a title="Protein targeting" href="http://en.wikipedia.org/wiki/Protein_targeting">targeted</a> 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 <a title="Fusion protein" href="http://en.wikipedia.org/wiki/Fusion_protein">fusion protein</a> or <a title="Chimera (protein)" href="http://en.wikipedia.org/wiki/Chimera_%28protein%29">chimera</a> consisting of the natural protein of interest linked to a &quot;<a title="Reporter gene" href="http://en.wikipedia.org/wiki/Reporter_gene">reporter</a>&quot; such as <a title="Green fluorescent protein" href="http://en.wikipedia.org/wiki/Green_fluorescent_protein">green fluorescent protein</a> (GFP). The fused protein's position within the cell can be cleanly and efficiently visualized using <a title="Microscopy" href="http://en.wikipedia.org/wiki/Microscopy">microscopy</a>, as shown in the figure opposite.</p><p>Through another genetic engineering application known as <a title="Site-directed mutagenesis" href="http://en.wikipedia.org/wiki/Site-directed_mutagenesis">site-directed mutagenesis</a>, researchers can alter the protein sequence and hence its structure, cellular localization, and susceptibility to regulation, which can be followed <em>in vivo</em> by GFP tagging or <em>in vitro</em> by <a title="Enzyme kinetics" href="http://en.wikipedia.org/wiki/Enzyme_kinetics">enzyme kinetics</a> and binding studies.</p>

<div class="noprint"><em>Main articles: <a title="Proteomics" href="http://en.wikipedia.org/wiki/Proteomics">Proteomics</a> and <a title="Bioinformatics" href="http://en.wikipedia.org/wiki/Bioinformatics">Bioinformatics</a></em></div>

<p>The total complement of proteins present at a time in a cell or cell type is known as its <a title="Proteome" href="http://en.wikipedia.org/wiki/Proteome">proteome</a>, and the study of such large-scale data sets defines the field of <a title="Proteomics" href="http://en.wikipedia.org/wiki/Proteomics">proteomics</a>, named by analogy to the related field of <a title="Genomics" href="http://en.wikipedia.org/wiki/Genomics">genomics</a>. Key experimental techniques in proteomics include <a title="Protein microarray" href="http://en.wikipedia.org/wiki/Protein_microarray">protein microarrays</a>, which allow the detection of the relative levels of a large number of proteins present in a cell, and <a title="Two-hybrid screening" href="http://en.wikipedia.org/wiki/Two-hybrid_screening">two-hybrid screening</a>, which allows the systematic exploration of <a title="Protein-protein interaction" href="http://en.wikipedia.org/wiki/Protein-protein_interaction">protein-protein interactions</a>. The total complement of biologically possible such interactions is known as the <a title="Interactome" href="http://en.wikipedia.org/wiki/Interactome">interactome</a>. A systematic attempt to determine the structures of proteins representing every possible fold is known as <a title="Structural genomics" href="http://en.wikipedia.org/wiki/Structural_genomics">structural genomics</a>.</p><p>The large amount of genomic and proteomic data available for a variety of organisms, including the <a title="Human genome" href="http://en.wikipedia.org/wiki/Human_genome">human genome</a>, allows researchers to efficiently identify <a title="Homology (biology)" href="http://en.wikipedia.org/wiki/Homology_%28biology%29">homologous</a> proteins in distantly related organisms by <a title="Sequence alignment" href="http://en.wikipedia.org/wiki/Sequence_alignment">sequence alignment</a>. <a title="Sequence profiling tool" href="http://en.wikipedia.org/wiki/Sequence_profiling_tool">Sequence profiling tools</a> can perform more specific sequence manipulations such as <a title="Restriction enzyme" href="http://en.wikipedia.org/wiki/Restriction_enzyme">restriction enzyme</a> maps, <a title="Open reading frame" href="http://en.wikipedia.org/wiki/Open_reading_frame">open reading frame</a> analyses for <a title="Nucleotide" href="http://en.wikipedia.org/wiki/Nucleotide">nucleotide</a> sequences, and <a title="Secondary structure" href="http://en.wikipedia.org/wiki/Secondary_structure">secondary structure</a> prediction. From this data <a title="Phylogenetic tree" href="http://en.wikipedia.org/wiki/Phylogenetic_tree">phylogenetic trees</a> can be constructed and <a title="Evolution" href="http://en.wikipedia.org/wiki/Evolution">evolutionary</a> hypotheses developed using special software like <a title="ClustalW" href="http://en.wikipedia.org/wiki/ClustalW">ClustalW</a> regarding the ancestry of modern organisms and the genes they express. The field of <a title="Bioinformatics" href="http://en.wikipedia.org/wiki/Bioinformatics">bioinformatics</a> seeks to assemble, annotate, and analyze genomic and proteomic data, applying <a title="Computer science" href="http://en.wikipedia.org/wiki/Computer_science">computational</a> techniques to biological problems such as <a title="Gene finding" href="http://en.wikipedia.org/wiki/Gene_finding">gene finding</a> and <a title="Cladistics" href="http://en.wikipedia.org/wiki/Cladistics">cladistics</a>.</p>

<p>Complementary to the field of structural genomics, <a title="Protein structure prediction" href="http://en.wikipedia.org/wiki/Protein_structure_prediction">protein structure prediction</a> 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 <a title="Homology modeling" href="http://en.wikipedia.org/wiki/Homology_modeling">homology modeling</a>, relies on the existence of a &quot;template&quot; 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 &quot;perfect&quot; sequence alignment is known.<sup class="reference" id="_ref-Zhang_0"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-Zhang">[17]</a></sup> Many structure prediction methods have served to inform the emerging field of <a title="Protein engineering" href="http://en.wikipedia.org/wiki/Protein_engineering">protein engineering</a>, in which novel protein folds have already been designed.<sup class="reference" id="_ref-Kuhlman_0"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-Kuhlman">[18]</a></sup> A more complex computational problem is the prediction of intermolecular interactions, such as in <a title="Molecular docking" href="http://en.wikipedia.org/wiki/Molecular_docking">molecular docking</a> and <a title="Protein-protein interaction prediction" href="http://en.wikipedia.org/wiki/Protein-protein_interaction_prediction">protein-protein interaction prediction</a>.</p><p>The processes of protein folding and binding can be simulated using techniques derived from <a title="Molecular dynamics" href="http://en.wikipedia.org/wiki/Molecular_dynamics">molecular dynamics</a>, which increasingly take advantage of <a title="Distributed computing" href="http://en.wikipedia.org/wiki/Distributed_computing">distributed computing</a> as in the <a title="Folding@Home" href="http://en.wikipedia.org/wiki/Folding%40Home">Folding@Home</a> project. The folding of small alpha-helical protein domains such as the <a title="Villin" href="http://en.wikipedia.org/wiki/Villin">villin</a> headpiece<sup class="reference" id="_ref-Zagrovic_0"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-Zagrovic">[19]</a></sup> and the <a title="HIV" href="http://en.wikipedia.org/wiki/HIV">HIV</a> accessory protein<sup class="reference" id="_ref-Herges_0"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-Herges">[20]</a></sup> have been successfully simulated <em>in silico</em>, and hybrid methods that combine standard molecular dynamics with <a title="Quantum mechanics" href="http://en.wikipedia.org/wiki/Quantum_mechanics">quantum mechanics</a> calculations have allowed exploration of the electronic states of <a title="Rhodopsin" href="http://en.wikipedia.org/wiki/Rhodopsin">rhodopsins</a>.<sup class="reference" id="_ref-Hoffmann_0"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-Hoffmann">[21]</a></sup></p>

<li><a title="PyMOL" href="http://en.wikipedia.org/wiki/PyMOL">PyMOL</a> </li> <li><a title="Sirius visualization software" href="http://en.wikipedia.org/wiki/Sirius_visualization_software">Sirius</a> </li> <li><a title="Rasmol" href="http://en.wikipedia.org/wiki/Rasmol">Rasmol</a> </li> <li><a title="Visual molecular dynamics" href="http://en.wikipedia.org/wiki/Visual_molecular_dynamics">Visual molecular dynamics</a> </li>

<dl><dd><em>Further information: <a title="Protein in nutrition" href="http://en.wikipedia.org/wiki/Protein_in_nutrition">Protein in nutrition</a></em> </dd></dl><p>Most <a title="Microorganism" href="http://en.wikipedia.org/wiki/Microorganism">microorganisms</a> and plants can biosynthesize all 20 standard <a title="Amino acids" href="http://en.wikipedia.org/wiki/Amino_acids">amino acids</a>, while animals must obtain some of the amino acids from the <a title="Diet (nutrition)" href="http://en.wikipedia.org/wiki/Diet_%28nutrition%29">diet</a>.<sup class="reference" id="_ref-Voet_1"><a title="" href="http://en.wikipedia.org/wiki/Protein#_note-Voet">[13]</a></sup> Key enzymes in the biosynthetic pathways that synthesize certain amino acids - such as <a title="Aspartokinase" href="http://en.wikipedia.org/wiki/Aspartokinase">aspartokinase</a>, which catalyzes the first step in the synthesis of <a title="Lysine" href="http://en.wikipedia.org/wiki/Lysine">lysine</a>, <a title="Methionine" href="http://en.wikipedia.org/wiki/Methionine">methionine</a>, and <a title="Threonine" href="http://en.wikipedia.org/wiki/Threonine">threonine</a> from <a title="Aspartate" href="http://en.wikipedia.org/wiki/Aspartate">aspartate</a> - are not present in animals. The amino acids that an organism cannot synthesize on its own are referred to as <a title="Essential amino acids" href="http://en.wikipedia.org/wiki/Essential_amino_acids">essential amino acids</a>. (This designation is often used to specifically identify those essential to <a title="Human" href="http://en.wikipedia.org/wiki/Human">humans</a>.) If amino acids are present in the environment, most microorganisms can conserve energy by taking up the amino acids from the environment and downregulating their own biosynthetic pathways. <a title="Bacteria" href="http://en.wikipedia.org/wiki/Bacteria">Bacteria</a> are often <a title="Genetic engineering" href="http://en.wikipedia.org/wiki/Genetic_engineering">engineered</a> in the laboratory to lack the genes necessary for synthesizing a particular amino acid, providing a <a title="Selectable marker" href="http://en.wikipedia.org/wiki/Selectable_marker">selectable marker</a> for the success of <a title="Transfection" href="http://en.wikipedia.org/wiki/Transfection">transfection</a>, or the introduction of foreign DNA.</p><p>In animals, amino acids are obtained through the consumption of foods containing protein. Ingested proteins are broken down through <a title="Digestion" href="http://en.wikipedia.org/wiki/Digestion">digestion</a>, which typically involves <a title="Denaturation (biochemistry)" href="http://en.wikipedia.org/wiki/Denaturation_%28biochemistry%29">denaturation</a> of the protein through exposure to <a title="Acid" href="http://en.wikipedia.org/wiki/Acid">acid</a> and degradation by the action of enzymes called <a title="Protease" href="http://en.wikipedia.org/wiki/Protease">proteases</a>. Ingestion of essential amino acids is critical to the health of the organism, since the biosynthesis of proteins that include these amino acids is inhibited by their low concentration. Amino acids are also an important dietary source of <a title="Nitrogen" href="http://en.wikipedia.org/wiki/Nitrogen">nitrogen</a>. Some ingested amino acids, especially those that are not essential, are not used directly for protein biosynthesis. Instead, they are converted to <a title="Carbohydrate" href="http://en.wikipedia.org/wiki/Carbohydrate">carbohydrates</a> through <a title="Gluconeogenesis" href="http://en.wikipedia.org/wiki/Gluconeogenesis">gluconeogenesis</a>, which is also used under <a title="Starvation" href="http://en.wikipedia.org/wiki/Starvation">starvation</a> conditions to generate <a title="Glucose" href="http://en.wikipedia.org/wiki/Glucose">glucose</a> from the body's own proteins, particularly those found in <a title="Muscle" href="http://en.wikipedia.org/wiki/Muscle">muscle</a>.</p>

<dl><dd><em>Further information: <a title="History of molecular biology" href="http://en.wikipedia.org/wiki/History_of_molecular_biology">History of molecular biology</a></em> </dd></dl><p>Proteins were recognized as a distinct class of biological molecules in the eighteenth century by <a title="Antoine François, comte de Fourcroy" href="http://en.wikipedia.org/wiki/Antoine_Fran%C3%A7ois%2C_comte_de_Fourcroy">Antoine Fourcroy</a> and others, distinguished by the molecules' ability to <a title="Coagulate" href="http://en.wikipedia.org/wiki/Coagulate">coagulate</a> or <a title="Flocculation" href="http://en.wikipedia.org/wiki/Flocculation">flocculate</a> under treatments with heat or acid. Noted examples at the time included albumen from <a title="Egg white" href="http://en.wikipedia.org/wiki/Egg_white">egg whites</a>, <a title="Blood" href="http://en.wikipedia.org/wiki/Blood">blood</a>, <a title="Serum albumin" href="http://en.wikipedia.org/wiki/Serum_albumin">serum albumin</a>, <a title="Fibrin" href="http://en.wikipedia.org/wiki/Fibrin">fibrin</a>, and <a title="Wheat gluten" href="http://en.wikipedia.org/wiki/Wheat_gluten">wheat gluten</a>. Dutch chemist <a title="Gerhardus Johannes Mulder" href="http://en.wikipedia.org/wiki/Gerhardus_Johannes_Mulder">Gerhardus Johannes Mulder</a> carried out <a title="Elemental analysis" href="http://en.wikipedia.org/wiki/Elemental_analysis">elemental analysis</a> of common proteins and found that nearly all proteins had the same <a title="Empirical formula" href="http://en.wikipedia.org/wiki/Empirical_formula">empirical formula</a>. The term &quot;protein&quot; to describe these molecules was proposed in 1838 by Mulder's associate <a title="Jöns Jakob Berzelius" href="http://en.wikipedia.org/wiki/J%C3%B6ns_Jakob_Berzelius">J&ouml;ns Jakob Berzelius</a>. Mulder went on to identify the products of protein degradation such as the <a title="Amino acid" href="http://en.wikipedia.org/wiki/Amino_acid">amino acid</a> <a title="Leucine" href="http://en.wikipedia.org/wiki/Leucine">leucine</a> for which he found a (nearly correct) molecular weight of 131 <a title="Atomic mass unit" href="http://en.wikipedia.org/wiki/Atomic_mass_unit">Da</a>.</p><p>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 <a title="Blood" href="http://en.wikipedia.org/wiki/Blood">blood</a>, <a title="Egg white" href="http://en.wikipedia.org/wiki/Egg_white">egg white</a>, various <a title="Toxin" href="http://en.wikipedia.org/wiki/Toxin">toxins</a>, and digestive/metabolic enzymes obtained from <a title="Slaughterhouse" href="http://en.wikipedia.org/wiki/Slaughterhouse">slaughterhouses</a>. In the late 1950s, the <a title="Armour and Company" href="http://en.wikipedia.org/wiki/Armour_and_Company">Armour Hot Dog Co.</a> purified 1 kg (= one million milligrams) of pure bovine pancreatic <a title="Ribonuclease A" href="http://en.wikipedia.org/wiki/Ribonuclease_A">ribonuclease A</a> and made it freely available to scientists around the world.</p><p><a title="Linus Pauling" href="http://en.wikipedia.org/wiki/Linus_Pauling">Linus Pauling</a> is credited with the successful prediction of regular protein <a title="Secondary structure" href="http://en.wikipedia.org/wiki/Secondary_structure">secondary structures</a> based on <a title="Hydrogen bonding" href="http://en.wikipedia.org/wiki/Hydrogen_bonding">hydrogen bonding</a>, an idea first put forth by <a title="William Astbury" href="http://en.wikipedia.org/wiki/William_Astbury">William Astbury</a> in 1933. Later work by <a class="new" title="Walter Kauzman" href="http://en.wikipedia.org/w/index.php?title=Walter_Kauzman&amp;action=edit">Walter Kauzman</a> on <a title="Denaturation" href="http://en.wikipedia.org/wiki/Denaturation">denaturation</a>, based partly on previous studies by <a title="Kaj Ulrik Linderstrom-Lang" href="http://en.wikipedia.org/wiki/Kaj_Ulrik_Linderstrom-Lang">Kaj Linderstrom-Lang</a>, contributed an understanding of <a title="Protein folding" href="http://en.wikipedia.org/wiki/Protein_folding">protein folding</a> and structure mediated by <a title="Hydrophobic core" href="http://en.wikipedia.org/wiki/Hydrophobic_core">hydrophobic interactions</a>. In 1949 <a title="Fred Sanger" href="http://en.wikipedia.org/wiki/Fred_Sanger">Fred Sanger</a> correctly determined the amino acid sequence of <a title="Insulin" href="http://en.wikipedia.org/wiki/Insulin">insulin</a>, thus conclusively demonstrating that proteins consisted of linear polymers of amino acids rather than branched chains, <a title="Colloid" href="http://en.wikipedia.org/wiki/Colloid">colloids</a>, or <a title="Cyclol" href="http://en.wikipedia.org/wiki/Cyclol">cyclols</a>. The first atomic-resolution structures of proteins were solved by <a title="X-ray crystallography" href="http://en.wikipedia.org/wiki/X-ray_crystallography">X-ray crystallography</a> in the 1960s and by <a title="Protein nuclear magnetic resonance spectroscopy" href="http://en.wikipedia.org/wiki/Protein_nuclear_magnetic_resonance_spectroscopy">NMR</a> in the 1980s. As of 2006, the <a title="Protein Data Bank" href="http://en.wikipedia.org/wiki/Protein_Data_Bank">Protein Data Bank</a> has nearly 40,000 atomic-resolution structures of proteins. In more recent times, <a title="Cryo-electron microscopy" href="http://en.wikipedia.org/wiki/Cryo-electron_microscopy">cryo-electron microscopy</a> of large macromolecular assemblies and computational <a title="Protein structure prediction" href="http://en.wikipedia.org/wiki/Protein_structure_prediction">protein structure prediction</a> of small protein <a title="Structural domain" href="http://en.wikipedia.org/wiki/Structural_domain">domains</a> are two methods approaching atomic resolution.</p>

<li><a title="Amino acid" href="http://en.wikipedia.org/wiki/Amino_acid">Amino acid</a> </li> <li><a title="Essential amino acid" href="http://en.wikipedia.org/wiki/Essential_amino_acid">Essential amino acid</a> </li> <li><a title="Protein design" href="http://en.wikipedia.org/wiki/Protein_design">Protein design</a> </li> <li><a title="Intein" href="http://en.wikipedia.org/wiki/Intein">Intein</a> </li> <li><a title="List of recombinant proteins" href="http://en.wikipedia.org/wiki/List_of_recombinant_proteins">List of recombinant proteins</a> </li> <li><a title="List of proteins" href="http://en.wikipedia.org/wiki/List_of_proteins">List of proteins</a> </li> <li><a title="Prion" href="http://en.wikipedia.org/wiki/Prion">Prion</a> </li> <li><a title="Edible protein per unit area of land" href="http://en.wikipedia.org/wiki/Edible_protein_per_unit_area_of_land">Edible protein per unit area of land</a> </li> <li><a title="Expression cloning" href="http://en.wikipedia.org/wiki/Expression_cloning">Expression cloning</a> </li>

<li id="_note-0"><strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-0">^</a></strong> <cite style="FONT-STYLE: normal">Sumner, JB (1926). &quot;<a class="external text" title="http://wwwThe Isolation and Crystallization of the Enzyme Urease.jbcPreliminary Paper&quot;.org/cgi/reprint<em>J Biol Chem</em> <strong>69</2/strong>: 435-41.pdf?ijkey</cite><span class=028d5e540dab50accbf86e01be08db51ef49008f" relZ3988" title="nofollow" hrefctx_ver="http://wwwZ39.jbc.org/cgi/reprint/69/2/435.pdf?ijkey88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=028d5e540dab50accbf86e01be08db51ef49008f">The +Isolation +and +Crystallization +of +the +Enzyme +Urease. +Preliminary +Paper</a>&quotamp;rft. <em>jtitle=J +Biol +Chem</em> <strong>69</strong>: 435-41&amp;rft.</cite><span classdate="Z3988" title="ctx_ver=Z39.88-20041926&amp;rft_val_fmtrft.volume=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal69&amp;rft.genreau=articleSumner%2C+JB&amp;rft.atitlepages=The+Isolation+and+Crystallization+of+the+Enzyme+Urease.+Preliminary+Paper435-41&amp;rftrft_id=http%3A%2F%2Fwww.jtitle=J+Biol+Chem&amp;rftjbc.date=1926&amp;rftorg%2Fcgi%2Freprint%2F69%2F2%2F435.volume=69pdf%3Fijkey%3D028d5e540dab50accbf86e01be08db51ef49008f">&ampnbsp;rft.au</span> </li> <li id=Sumner%2C+JB&amp;rft.pages=435"_note-41&amp;rft_id=http%3A%2F%2Fwww.jbc.org%2Fcgi%2Freprint%2F69%2F2%2F435.pdf%3Fijkey%3D028d5e540dab50accbf86e01be08db51ef49008f">&nbsp;1"><strong>^</spanstrong> </li> <li idcite style="_noteFONT-1STYLE: normal"><strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-1">^</a></strong> <cite style="FONT-STYLE: normal">Muirhead H, Perutz M (1963)Muirhead H, Perutz M (1963). &quot;Structure of haemoglobin. A three-dimensional fourier synthesis of reduced human haemoglobin at 5.5 A resolution&quot;. <em>Nature</em> <strong>199</strong> (4894): 633-8. PMID 14074546. <a /cite><span class="externalZ3988" title="http://wwwctx_ver=Z39.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve88-2004&amp;dbrft_val_fmt=pubmedinfo%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;doptrft.genre=Abstractarticle&amp;list_uidsrft.atitle=14074546" href="http://wwwStructure+of+haemoglobin.ncbi+A+three-dimensional+fourier+synthesis+of+reduced+human+haemoglobin+at+5.nlm5+A+resolution&amp;rft.nihjtitle=Nature&amp;rft.gov/entrez/query.fcgi?cmddate=Retrieve1963&amp;dbrft.volume=pubmed199&amp;doptrft.issue=Abstract4894&amp;list_uidsrft.au=Muirhead+H%2C+Perutz+M&amp;rft.pages=633-8&amp;rft_id=info:pmid/14074546">PMID 14074546">&nbsp;</aspan>.</citeli> <span classli id="Z3988_note-2" title><strong>^</strong> <cite style="ctx_ver=Z39.88FONT-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rftSTYLE: normal">Kendrew J, Bodo G, Dintzis H, Parrish R, Wyckoff H, Phillips D (1958).genre=article&ampquot;rft.atitle=Structure+of+haemoglobin.+A+threeA three-dimensional+fourier+synthesis+model of+reduced+human+haemoglobin+at+5.5+A+resolution&ampthe myoglobin molecule obtained by x-ray analysis&quot;rft.jtitle=<em>Nature&amp;rft</em> <strong>181</strong> (4610): 662-6.datePMID 13517261.</cite><span class="Z3988" title="ctx_ver=1963&amp;rftZ39.volume=19988-2004&amp;rft.issuerft_val_fmt=4894&ampinfo%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.augenre=Muirhead+H%2C+Perutz+Marticle&amp;rft.pagesatitle=633A+three-8&amp;rft_id=info:pmid/14074546">dimensional+model+of+the+myoglobin+molecule+obtained+by+x-ray+analysis&nbspamp;</span> </li> <li idrft.jtitle=Nature&amp;rft.date="_note-2"><strong><a title1958&amp;rft.volume="" href181&amp;rft.issue="http://en4610&amp;rft.wikipedia.org/wiki/Protein#_ref-2">^</a></strong> <cite styleau="FONT-STYLE: normal">Kendrew J, Kendrew+J%2C+Bodo +G, %2C+Dintzis +H, %2C+Parrish +R, %2C+Wyckoff +H, %2C+Phillips +D (1958). &quotamp;A threerft.pages=662-dimensional model of the myoglobin molecule obtained by x-ray analysis6&quotamp;. <emrft_id=info:pmid/13517261">Nature&nbsp;</emspan> </li> <li id="_note-3"> <strong>181^</strong> Nelson, D. L. and Cox, M. M. (46102005): 662-6Lehninger's Principles of Biochemistry, 4th Edition, W. H. Freeman and Company, New York. <a class/li> <li id="external_note-Lodish" title="http:>^ <sup><em><strong>a</strong></em></www.ncbi.nlm.nih.govsup> ^{<em><strong>b</entrezstrong></query.fcgi?cmd=Retrieve&amp;db=pubmed&amp;dopt=Abstract&amp;list_uids=13517261" href="http:em>} <sup><em><strong>c</www.ncbi.nlm.nih.govstrong></entrez/query.fcgi?cmd=Retrieve&amp;db=pubmed&amp;dopt=Abstract&amp;list_uids=13517261"em>PMID 13517261</asup>Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipurksy SL, Darnell J.</cite><span class="Z3988" title="ctx_ver=Z39.88-(2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft). <em>Molecular Cell Biology</em> 5th ed.genre=article&amp;rftWH Freeman and Company: New York, NY.atitle</li> <li id=A+three"_note-dimensional+model+of+the+myoglobin+molecule+obtained+by+x-ray+analysis&amp;rftDobson"><strong>^</strong> Dobson CM.jtitle=Nature&amp;rft(2000).date=1958&amp;rftThe nature and significance of protein folding.volume=181&amp;rftIn <em>Mechanisms of Protein Folding</em> 2nd ed. Ed.issue=4610&amp;rftRH Pain.au=Kendrew+J%2C+Bodo+G%2C+Dintzis+H%2C+Parrish+R%2C+Wyckoff+H%2C+Phillips+D&amp;rft.pages<em>Frontiers in Molecular Biology</em> series. Oxford University Press: New York, NY. </li> <li id=662"_note-6&amp;rft_id=info:pmid/135172614">&nbsp;</spanstrong> ^</listrong> <li idcite style="_noteFONT-3STYLE: normal"><strong><Fulton A, Isaacs W (1991). &quot;Titin, a title="" href="http://enhuge, elastic sarcomeric protein with a probable role in morphogenesis&quot;.wikipedia.org/wiki/Protein#_ref-3"<em>^Bioessays</aem></strong> Nelson, D. L. and Cox, M. M. 13</strong> (20054) Lehninger's Principles of Biochemistry, 4th Edition, W: 157-61. HPMID 1859393. Freeman and Company, New York. <</licite> <li idspan class="_note-LodishZ3988">^ <a title="" hrefctx_ver="http://enZ39.wikipedia.org/wiki/Protein#_ref88-Lodish_0">^{<em><strong>a</strong></em>}</a> <a title2004&amp;rft_val_fmt="" hrefinfo%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre="http://enarticle&amp;rft.wikipedia.org/wiki/Protein#_ref-Lodish_1">^{<em><strong>b</strong></em>}</atitle=Titin%2C+a+huge%2C+elastic+sarcomeric+protein+with+a> <a title+probable+role+in+morphogenesis&amp;rft.jtitle="" hrefBioessays&amp;rft.date="http://en1991&amp;rft.wikipedia.org/wiki/Protein#_refvolume=13&amp;rft.issue=4&amp;rft.au=Fulton+A%2C+Isaacs+W&amp;rft.pages=157-Lodish_2"61&amp;rft_id=info:pmid/1859393">&nbsp;<sup/span><em/li> <strongli id="_note-5">c</strong>^</emstrong></supcite style="FONT-STYLE: normal"></a> Lodish HBruckdorfer T, Berk AMarder O, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipurksy SL, Darnell J. (2004)Albericio F (2004). &quot;From production of peptides in milligram amounts for research to multi-tons quantities for drugs of the future&quot;. <em>Molecular Cell BiologyCurr Pharm Biotechnol</em> 5th ed<strong>5</strong> (1): 29-43. WH Freeman and Company: New York, NYPMID 14965208. </licite> <li idspan class="_note-DobsonZ3988"><strong><a title="" hrefctx_ver="http://enZ39.wikipedia.org/wiki/Protein#_ref88-Dobson_0">^</a></strong> Dobson CM2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft. (2000)genre=article&amp;rft. The nature and significance atitle=From+production+of protein folding. In <em>Mechanisms +peptides+in+milligram+amounts+for+research+to+multi-tons+quantities+for+drugs+of Protein Folding</em> 2nd ed+the+future&amp;rft. Edjtitle=Curr+Pharm+Biotechnol&amp;rft. RH Paindate=2004&amp;rft. <em>Frontiers in Molecular Biology</em> seriesvolume=5&amp;rft. Oxford University Press: New York, NYissue=1&amp;rft. </li> <li idau="_noteBruckdorfer+T%2C+Marder+O%2C+Albericio+F&amp;rft.pages=29-443&amp;rft_id=info:pmid/14965208">&nbsp;<strong/span><a title/li> <li id="" href="http://en.wikipedia.org/wiki/Protein#_ref_note-46">^</astrong>^</strong> <cite style="FONT-STYLE: normal">Fulton ASchwarzer D, Isaacs W Cole P (19912005). &quot;Titin, Protein semisynthesis and expressed protein ligation: chasing a huge, elastic sarcomeric protein with a probable role in morphogenesis's tail&quot;. <em>BioessaysCurr Opin Chem Biol</em> <strong>139</strong> (46): 157561-619. <a PMID 16226484.</cite><span class="externalZ3988" title="http://wwwctx_ver=Z39.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve88-2004&amp;dbrft_val_fmt=pubmedinfo%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;doptrft.genre=Abstractarticle&amp;list_uids=1859393" href="http://wwwrft.ncbi.nlm.nih.gov/entrez/query.fcgi?cmdatitle=Retrieve&amp;db=pubmed&amp;dopt=AbstractProtein+semisynthesis+and+expressed+protein+ligation%3A+chasing+a+protein%27s+tail&amp;list_uids=1859393">PMID 1859393</a>rft.</cite><span classjtitle="Z3988" title="ctx_ver=Z39.88-2004Curr+Opin+Chem+Biol&amp;rft_val_fmtrft.date=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal2005&amp;rft.genrevolume=article9&amp;rft.atitleissue=Titin%2C6&amp;rft.au=Schwarzer+a+hugeD%2C+elasticCole+sarcomeric+protein+with+a+probable+role+in+morphogenesisP&amp;rft.jtitlepages=Bioessays561-9&amp;rft.date=1991rft_id=info:pmid/16226484">&ampnbsp;rft.volume</span> </li> <li id=13&amp;rft.issue=4&amp;rft.au=Fulton+A%2C+Isaacs+W&amp;rft.pages=157-61&amp;rft_id=info:pmid"_note-Branden">^ <sup><em><strong>a</strong></em></1859393"sup> <sup>&nbsp;</spanem> </li> <li id="_note-5"strong>b</strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-5"em>^</asup></strongBranden C, Tooze J. (1999). <em> Introduction to Protein Structure<cite style/em> 2nd ed. Garland Publishing: New York, NY </li> <li id="FONT_note-STYLE: normal7">Bruckdorfer <strong>^</strong> Gonen T, Marder OCheng Y, Sliz P, Hiroaki Y, Fujiyoshi Y, Harrison SC, Albericio F Walz T. (20042005). &quot;From production of peptides Lipid-protein interactions in milligram amounts for research to multidouble-layered two-tons quantities for drugs of the future&quot;dimensional AQP0 crystals. <em>Curr Pharm BiotechnolNature</em> <strong>5</strong> (1438(7068): 29633-438. <a class/li> <li id="external_note-8" title="http:><strong>^<//wwwstrong> Walian P, Cross TA, Jap BK.ncbi(2004).nlmStructural genomics of membrane proteins <em>Genome Biol</em> 5(4): 215.nih.gov</entrez/query.fcgi?cmd=Retrieve&amp;db=pubmed&amp;dopt=Abstract&amp;list_uidsli> <li id=14965208" href=_note-Voet"http:>^ ^{<em><strong>a</strong></www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=pubmed&amp;dopt=Abstract&amp;list_uids=14965208"em>PMID 14965208</asup>.</citesup><span class="Z3988" title="ctx_ver=Z39em><strong>b</strong></em>} Voet D, Voet JG.88-(2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft). <em>Biochemistry</em> Vol 1 3rd ed.genre=article&amp;rftWiley: Hoboken, NJ.atitle</li> <li id=From+production+of+peptides+in+milligram+amounts+for+research+to+multi"_note-tons+quantities+for+drugs+of+the+future9"><strong>^</strong> <cite style="FONT-STYLE: normal">Bairoch A. (2000). &ampquot;rft.jtitle=Curr+Pharm+BiotechnolThe ENZYME database in 2000&ampquot;rft.date=2004&amp;rft.volume=5&amp;rft.issue=1&amp;rft.au=Bruckdorfer+T%2C+Marder+O%2C+Albericio+F&amp;rft.pages=29-43&amp;rft_id=info:pmid/14965208">&nbsp;</span> </li> <li id="_note-6"><strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-6">^</a></strong> <cite style="FONT-STYLE: normal">Schwarzer D, Cole P (2005). &quot;Protein semisynthesis and expressed protein ligation: chasing a protein's tail&quot;. <em>Curr Opin Chem Biol</em> <strong>9</strong> (6): 561-9. <a class="external" title="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=pubmed&amp;dopt=Abstract&amp;list_uids=16226484" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=pubmed&amp;dopt=Abstract&amp;list_uids=16226484">PMID 16226484</a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Protein+semisynthesis+and+expressed+protein+ligation%3A+chasing+a+protein%27s+tail&amp;rft.jtitle=Curr+Opin+Chem+Biol&amp;rft.date=2005&amp;rft.volume=9&amp;rft.issue=6&amp;rft.au=Schwarzer+D%2C+Cole+P&amp;rft.pages=561-9&amp;rft_id=info:pmid/16226484">&nbsp;</span> </li> <li id="_note-Branden">^ <a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-Branden_0">^{<em><strong>a</strong></em>}</a> <a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-Branden_1">^{<em><strong>b</strong></em>}</a> Branden C, Tooze J. (1999). <em>Introduction to Protein Structure</em> 2nd ed. Garland Publishing: New York, NY </li> <li id="_note-7"><strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-7">^</a></strong> Gonen T, Cheng Y, Sliz P, Hiroaki Y, Fujiyoshi Y, Harrison SC, Walz T. (2005). Lipid-protein interactions in double-layered two-dimensional AQP0 crystals. <em>Nature</em> 438(7068):633-8. </li> <li id="_note-8"><strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-8">^</a></strong> Walian P, Cross TA, Jap BK. (2004). Structural genomics of membrane proteins <em>Genome Biol</em> 5(4): 215. </li> <li id="_note-Voet">^ <a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-Voet_0">^{<em><strong>a</strong></em>}</a> <a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-Voet_1">^{<em><strong>b</strong></em>}</a> Voet D, Voet JG. (2004). <em>Biochemistry</em> Vol 1 3rd ed. Wiley: Hoboken, NJ. </li> <li id="_note-9"><strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-9">^</a></strong> <cite style="FONT-STYLE: normal">Bairoch A. (2000). &quot;<a class="external text" title="http://www.expasy.org/NAR/enz00.pdf" rel="nofollow" href="http://www.expasy.org/NAR/enz00.pdf">The ENZYME database in 2000</a>&quot;. <em>Nucleic Acids Res</em> <<em>Nucleic Acids Res</em> <strong>28</strong>: 304-305. <a class="external" title="http:28<//www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=pubmed&amp;dopt=Abstract&amp;list_uids=10592255" href="httpstrong>://www.ncbi.nlm.nih.gov/entrez/query304-305.fcgi?cmd=Retrieve&amp;db=pubmed&amp;dopt=Abstract&amp;list_uids=10592255">PMID 10592255</a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+ENZYME+database+in+2000&amp;rft.jtitle=Nucleic+Acids+Res&amp;rft.date=2000&amp;rft.volume=28&amp;rft.au=Bairoch+A.&amp;rft.pages=304-305&amp;rft_id=http%3A%2F%2Fwww.expasy.org%2FNAR%2Fenz00.pdf">&nbsp;</span> </li> <li id="_note-10"><strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-10">^</a></strong> <cite style="FONT-STYLE: normal">Radzicka A, Wolfenden R. (1995). &quot;A proficient enzyme.&quot;. <em>Science</em> <strong>6</strong> (267): 90-931. <a class="external" title="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=pubmed&amp;dopt=Abstract&amp;list_uids=7809611" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=pubmed&amp;dopt=Abstract&amp;list_uids=7809611">PMID 7809611</a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=A+proficient+enzyme.&amp;rft.jtitle=Science&amp;rft.date=1995&amp;rft.volume=6&amp;rft.issue=267&amp;rft.au=Radzicka+A%2C+Wolfenden+R.&amp;rft.pages=90-931">&nbsp;</span> </li> <li id="_note-11"><strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-11">^</a></strong> <a class="external text" title="http://www.ebi.ac.uk/thornton-srv/databases/CSA/" rel="nofollow" href="http://www.ebi.ac.uk/thornton-srv/databases/CSA/">The Catalytic Site Atlas at The European Bioinformatics Institute</a> </li> <li id="_note-Zhang"><strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-Zhang_0">^</a></strong> Zhang Y, Skolnick J. (2005). The protein structure prediction problem could be solved using the current PDB library. <em>Proc Natl Acad Sci USA</em> 102(4):1029-34. </li> <li id="_note-Kuhlman"><strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-Kuhlman_0">^</a></strong> Kuhlman B, Dantas G, Ireton GC, Varani G, Stoddard BL, Baker D. (2003). Design of a novel globular protein fold with atomic-level accuracy. <em>Science</em> 302(5649):1364-8. </li> <li id="_note-Zagrovic"><strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-Zagrovic_0">^</a></strong> Zagrovic B, Snow CD, Shirts MR, Pande VS. (2002). Simulation of folding of a small alpha-helical protein in atomistic detail using worldwide-distributed computing. <em>J Mol Biol</em> 323(5):927-37. </li> <li id="_note-Herges"><strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-Herges_0">^</a></strong> Herges T, Wenzel W. (2005). In silico folding of a three helix protein and characterization of its free-energy landscape in an all-atom force field. <em>Phys Rev Let</em> 94(1):018101. </li> <li id="_note-Hoffmann"><strong><a title="" href="http://en.wikipedia.org/wiki/Protein#_ref-Hoffmann_0">^</a></strong> Hoffmann M, Wanko M, Strodel P, Konig PH, Frauenheim T, Schulten K, Thiel W, Tajkhorshid E, Elstner M. (2006). Color tuning in rhodopsins: the mechanism for the spectral shift between bacteriorhodopsin and sensory rhodopsin II. <em>J Am Chem Soc</em> 128(33):10808-18. </li>

<li><a class="external text" title="http://www3.interscience.wiley.com/cgi-bin/jhome/36176?CRETRY=1&amp;SRETRY=0" rel="nofollow" href="http://www3.interscience.wiley.com/cgi-bin/jhome/36176?CRETRY=1&amp;SRETRY=0">Proteins (the journal)</a>, also called &quot;Proteins: Structure, Function, and Bioinformatics&quot; and previously &quot;Proteins: Structure, Function, and Genetics&quot; (<a title="1986" href="http://en.wikipedia.org/wiki/1986">1986</a>-<a title="1995" href="http://en.wikipedia.org/wiki/1995">1995</a>). </li>