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Protein
Proteins are large biomolecules and macromolecules that
comprise 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, providing structure to cells and
organisms, 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 3D 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 A representation of the 3D structure of
the protein myoglobin showing turquoise
considered to be proteins and are commonly called peptides.
α-helices. This protein was the first to
The individual amino acid residues are bonded together by have its structure solved by X-ray
peptide bonds and adjacent amino acid residues. The crystallography. Toward the right-center
sequence of amino acid residues in a protein is defined by the among the coils, a prosthetic group
sequence of a gene, which is encoded in the genetic code. In called a heme group (shown in gray) with
general, the genetic code specifies 20 standard amino acids; a bound oxygen molecule (red).
but 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. Some require a non-protein chemical compound
or ion for biological activity, these are known as cofactors. Proteins can 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 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 or misfolded proteins are degraded more rapidly, often by the
proteasome, which is a large protein assembly itself. These proteins are degraded either due to being
targeted (ubiquitin ligases can mark a protein for destruction) or due to being unstable or damaged.

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. Some proteins have structural or
mechanical functions, such as actin and myosin in muscle, and the cytoskeleton's scaffolding proteins
that maintain cell shape. Other proteins are important in cell signaling, immune responses, cell

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adhesion, and the cell cycle. In animals, proteins are needed in the diet to provide the essential amino
acids that cannot be made. Dietary proteins are digested into amino acids to replenish the body's free
amino acid pool, which is mostly used to make new body proteins, but is also critically important for
energy production and to make other vital nitrogen-containing molecules.

History and etymology

Discovery and early studies

Proteins have been studied and recognized since the 1700s by Antoine Fourcroy and others,[1][2] who
often collectively called them "albumins", or "albuminous materials" (Eiweisskörper, in German).[2]
Gluten, for example, was first separated from wheat in published research around 1747, and later
determined to exist in many plants.[1] In 1789, Antoine Fourcroy recognized three distinct varieties of
animal proteins: albumin, fibrin, and gelatin.[3] Vegetable (plant) proteins studied in the late 1700s
and early 1800s included gluten, plant albumin, gliadin, and legumin.[1]

Proteins were first described by the Dutch chemist Gerardus Johannes Mulder and named by the
Swedish chemist Jöns Jacob Berzelius in 1838.[4][5] Mulder carried out elemental analysis of common
proteins and found that nearly all proteins had the same empirical formula, C400H620N100O120P1S1.[6]
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",[7] "in the
lead", or "standing in front",[2] + -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.[6]

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".[8] Around 1862, Karl Heinrich Ritthausen isolated the amino acid glutamic
acid.[9] Thomas Burr Osborne compiled a detailed review of the vegetable proteins at the Connecticut
Agricultural Experiment Station. Osborne, alongside Lafayette Mendel, established several
nutritionally essential amino acids in feeding experiments with laboratory rats.[10] Diets lacking an
essential amino acid stunts the rats' growth, consistent with Liebig's law of the minimum.[11] The final
essential amino acid to be discovered, threonine, was identified by William Cumming Rose.[12]

The difficulty in purifying proteins impeded work by early protein biochemists. Proteins could be
obtained in large quantities from blood, egg whites, and keratin, but individual proteins were
unavailable. In the 1950s, the Armour Hot Dog Company purified 1 kg of 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.[6]

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Polypeptides
The understanding of proteins as polypeptides, or chains of
amino acids, came through the work of Franz Hofmeister and
Hermann Emil Fischer in 1902.[13][14] The central role of
proteins as enzymes in living organisms that catalyzed
reactions was not fully appreciated until 1926, when James B.
Sumner showed that the enzyme urease was in fact a
protein.[15]

Linus Pauling is credited with the successful prediction of

regular protein secondary structures based on hydrogen Polypeptide
[16]
bonding, an idea first put forth by William Astbury in 1933.
Later work by Walter Kauzmann on denaturation,[17][18]
based partly on previous studies by Kaj Linderstrøm-Lang,[19] contributed an understanding of
protein folding and structure mediated by hydrophobic interactions.[20]

The first protein to have its amino acid chain 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.[21] He won the Nobel Prize for this achievement in 1958.[22] Christian Anfinsen's studies of
the oxidative folding process of ribonuclease A, for which he won the nobel prize in 1972, solidified the
thermodynamic hypothesis of protein folding, according to which the folded form of a protein
represents its free energy minimum.[23][24]

Structure
With the development of X-ray crystallography, it
became possible to determine protein structures as well
as their sequences.[25] The first protein structures to be
solved were hemoglobin by Max Perutz and myoglobin
by John Kendrew, in 1958.[26][27] The use of computers
and increasing computing power has supported the
sequencing of complex proteins. In 1999, Roger
Kornberg sequenced the highly complex structure of
RNA polymerase using high intensity X-rays from
synchrotrons.[25]
John Kendrew with model of myoglobin in
progress
Since then, cryo-electron microscopy (cryo-EM) of large
macromolecular assemblies[28] has been developed.
Cryo-EM uses protein samples that are frozen rather than crystals, and beams of electrons rather than
X-rays. It causes less damage to the sample, allowing scientists to obtain more information and
analyze larger structures.[25] Computational protein structure prediction of small protein structural
domains[29] has helped researchers to approach atomic-level resolution of protein structures. As of
April 2024, the Protein Data Bank contains 181,018 X-ray, 19,809 EM and 12,697 NMR protein
structures.[30]

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Classification
Proteins are primarily classified by sequence and structure, although other classifications are
commonly used. Especially for enzymes the EC number system provides a functional classification
scheme.[31] Similarly, gene ontology classifies both genes and proteins by their biological and
biochemical function, and by their intracellular location.[32]

Sequence similarity is used to classify proteins both in terms of evolutionary and functional similarity.
This may use either whole proteins or protein domains, especially in multi-domain proteins. Protein
domains allow protein classification by a combination of sequence, structure and function, and they
can be combined in many ways. In an early study of 170,000 proteins, about two-thirds were assigned
at least one domain, with larger proteins containing more domains (e.g. proteins larger than 600
amino acids having an average of more than 5 domains).[33]

Biochemistry
Most proteins consist of linear polymers built
from series of up to 20 L-α-amino acids. All
proteinogenic amino acids have a common
structure where an α-carbon is bonded to an
amino group, a carboxyl group, and a variable
side chain. Only proline differs from this basic
structure as its side chain is cyclical, bonding to
the amino group, limiting protein chain
flexibility.[34] The side chains of the standard
amino acids have a variety of chemical structures
and properties, and it is the combined effect of all
amino acids that determines its three-
dimensional structure and chemical
reactivity. [35] Chemical structure of the peptide bond (bottom) and
the three-dimensional structure of a peptide bond
The amino acids in a polypeptide chain are linked between an alanine and an adjacent amino acid
(top/inset). The bond itself is made of the CHON
by peptide bonds between amino and carboxyl
elements.
group. An individual amino acid in a chain is
called a residue, and the linked series of carbon,
nitrogen, and oxygen atoms are known as the
main chain or protein backbone.[36]: 19 The
peptide bond has two resonance forms that
confer some double-bond character to the
backbone. The alpha carbons are roughly
coplanar with the nitrogen and the carbonyl
Resonance structures of the peptide bond that links
(C=O) group. The other two dihedral angles in individual amino acids to form a protein polymer
the peptide bond determine the local shape
assumed by the protein backbone. One
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consequence of the N-C(O) double bond character is that proteins are somewhat rigid.[36]: 31 A
polypeptide chain ends with a free amino group, known as the N-terminus or amino terminus, and a
free carboxyl group, known as the C-terminus or carboxy terminus.[37] By convention, peptide
sequences are written N-terminus to C-terminus, correlating with the order in which proteins are
synthesized by ribosomes.[37][38]

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 3D
structure. But the boundary between the two is not well defined and usually lies near 20–30
residues.[39]

Proteins can interact with many types of molecules and ions, including with other proteins, with
lipids, with carbohydrates, and with DNA.[40][41][42]

Abundance in cells
A typical bacterial cell, e.g. E. coli and Staphylococcus aureus, is estimated to contain about 2 million
proteins. Smaller bacteria, such as Mycoplasma or spirochetes contain fewer molecules, 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 have been estimated to contain about 50 million protein molecules and
human cells on the order of 1 to 3 billion.[43] The concentration of individual protein copies ranges
from a few molecules per cell up to 20 million.[44] Not all genes coding proteins are expressed in most
cells and their number depends on, for example, cell type and external stimuli. For instance, of the
20,000 or so proteins encoded by the human genome, only 6,000 are detected in lymphoblastoid
cells.[45] The most abundant protein in nature is thought to be RuBisCO, an enzyme that catalyzes the
incorporation of carbon dioxide into organic matter in photosynthesis. Plants can consist of as much
as 1% by weight of this enzyme.[46]

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
A ribosome produces a protein using
code, with some amino acids specified by more than one
mRNA as template.
codon.[42]: 1002–42 Genes encoded in DNA are first transcribed

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into pre-messenger RNA (mRNA) by proteins such as RNA

polymerase. Most organisms then process the pre-mRNA (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 The DNA sequence of a gene
soon as it is produced, or be bound by a ribosome after having encodes the amino acid sequence of a
moved away from the nucleoid. In contrast, eukaryotes make protein
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.[47]

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.[42]: 1002–42

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 with the unit dalton (Da), or its derivative unit
kilodalton (kDa). The average size of a protein increases from Archaea to Bacteria to Eukaryote (283,
311, 438 residues and 31, 34, 49 kDa respectively) due to a bigger number of protein domains
constituting proteins in higher organisms.[48] For instance, yeast proteins are on average 466 amino
acids long and 53 kDa in mass.[39] The largest known proteins are the titins, a component of the
muscle sarcomere, with a molecular mass of almost 3000 kDa and a total length of almost 27 000
amino acids.[49]

Chemical synthesis
Short proteins can be synthesized chemically by a family of
peptide synthesis methods. These rely on organic synthesis
techniques such as chemical ligation to produce peptides in
high yield.[50] 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,
Peptide synthesis
(this can also be achieved via genetic engineering when
producing recombinant proteins). [51] [52] 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.[53]

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Structure
Most proteins fold into unique 3D structures. The
shape into which a protein naturally folds is
known as its native conformation.[36]: 36
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.[36]: 37
Biochemists often refer to four distinct aspects of
The crystal structure of the chaperonin, a huge
a protein's structure:[36]: 30–34 protein complex. A single protein subunit is highlighted.
Chaperonins assist protein folding.
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 distinct
secondary structure can be present in the
same protein molecule.
Tertiary structure: the overall shape of a
single protein molecule; the spatial Three possible representations of the three-
relationship of the secondary structures to dimensional structure of the protein triose phosphate
one another. Tertiary structure is generally isomerase. Left: All-atom representation colored by
stabilized by nonlocal interactions, most atom type. Middle: Simplified representation illustrating
commonly the formation of a hydrophobic the backbone conformation, colored by secondary
core, but also through salt bridges, hydrogen structure. Right: Solvent-accessible surface
bonds, disulfide bonds, and even post- representation colored by residue type (acidic residues
translational modifications. The term "tertiary red, basic residues blue, polar residues green, nonpolar
structure" is often used as synonymous with residues white).
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.
Quinary structure: the signatures of protein surface that organize the crowded cellular interior.
Quinary structure is dependent on transient, yet essential, macromolecular interactions that occur
inside living cells.
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, protein structures vary because of
thermal vibration and collisions with other molecules.[42]: 368–75

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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 Molecular surface of several proteins showing their
comparative sizes. From left to right are: immunoglobulin
collagen, the major component of connective
G (IgG, an antibody), hemoglobin, insulin (a hormone),
tissue, or keratin, the protein component of hair
adenylate kinase (an enzyme), and glutamine
and nails. Membrane proteins often serve as synthetase (an enzyme).
receptors or provide channels for polar or
charged molecules to pass through the cell
membrane.[42]: 165–85

A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack
and hence promoting their own dehydration, are called dehydrons.[54]

Protein domains
Many proteins are composed of several protein domains, i.e. segments of a protein that fold into
distinct structural units.[55]: 134 Domains usually have specific functions, such as enzymatic activities
(e.g. kinase) or they serve as binding modules.[55]: 155–156

Protein domains vs. motifs. Protein domains (such as the EVH1 domain) are functional units within proteins that
fold into defined 3D structures. Motifs are usually short sequences with specific functions but without a stable 3D
structure. Many motifs are binding sites for other proteins (such as the red and green bars shown here in the context
of a VASP protein).[56]

Sequence motif
Short amino acid sequences within proteins often act as recognition sites for other proteins.[57] For
instance, SH3 domains typically bind to short PxxP motifs (i.e. 2 prolines [P], separated by two
unspecified amino acids [x], although the surrounding amino acids may determine the exact binding
specificity). Many such motifs has been collected in the Eukaryotic Linear Motif (ELM) database.[58]

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Cellular functions
Proteins are the chief actors within the cell, said to be carrying out the duties specified by the
information encoded in genes.[39] 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.[59] The set of proteins expressed in a particular cell or cell type is known as its
proteome.[55]: 120

The chief characteristic of proteins that 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 The enzyme hexokinase is shown as
specific; for example, the ribonuclease inhibitor protein binds a conventional ball-and-stick molecular
to human angiogenin with a sub-femtomolar dissociation model. To scale in the top right-hand
(< 10 −15 M) but does not bind at all to its amphibian
constant corner are two of its substrates, ATP and
homolog onconase (> 1 M). Extremely minor chemical glucose.
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.[60]

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 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 bind to, or be integrated into, cell membranes. The
ability of binding partners to induce conformational changes in proteins allows the construction of
enormously complex signaling networks.[42]: 830–49 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.[61][62]

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
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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.[63] 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).[64]

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.[65] The region of the enzyme that binds the substrate and contains the catalytic
residues is known as the active site.[55]: 389

Dirigent proteins are members of a class of proteins that dictate the stereochemistry of a compound
synthesized by other enzymes.[66]

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.[41]: 251–81

Antibodies are protein components of an adaptive immune system

whose main function is to bind antigens, or foreign substances in the
Ribbon diagram of a mouse
body, and target them for destruction. Antibodies can be secreted into antibody against cholera that
the extracellular environment or anchored in the membranes of binds a carbohydrate antigen
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.[42]: 275–50

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, and 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.[42]: 222–29 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.[67] Receptors are highly specific binding proteins, and many
hormones act by binding specifically to their receptors.[68]

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Transmembrane proteins can 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.[41]: 232–34

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.[42]: 178–81 Some
globular proteins can 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
Protein structure
cytoskeleton, which allows the cell to maintain its shape and
size.[55]: 490

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 generate the forces exerted by contracting muscles[42]: 258–64, 272 and play essential roles in
intracellular transport.[55]: 481, 490

Methods of study
Methods commonly used to study protein structure and function include immunohistochemistry, site-
directed mutagenesis, X-ray crystallography, nuclear magnetic resonance and mass spectrometry. 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:[69] for example, enzyme kinetics studies explore the chemical mechanism of an enzyme's
catalytic activity and its relative affinity for various possible substrate molecules.[70] 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, and can often provide more information about protein behavior in
different contexts.[71] In silico studies use computational methods to study proteins.[72]

Protein purification
Proteins may be purified from other cellular components using a variety of techniques such as
ultracentrifugation, precipitation, electrophoresis, and chromatography;[36]: 21–24 the advent of
genetic engineering has made possible a number of methods to facilitate purification.[73]

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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.[36]: 21–24 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 to their charge using electrofocusing.[74]

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 tags have been developed to help
researchers purify specific proteins from complex mixtures.[73]

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).[75] The fused
protein's position within the cell can then be cleanly and efficiently visualized using microscopy.[76]

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.[77]

Other possibilities exist, as well. For example, immunohistochemistry usually uses 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.[78]
Another applicable technique is cofractionation in sucrose (or other material) gradients using
isopycnic centrifugation.[79] While this technique does not prove colocalization of a compartment of
known density and the protein of interest, it indicates an increased likelihood.[79]

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Finally, the gold-standard method of cellular

localization is immunoelectron microscopy. This
technique 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.[80]

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,[81] and may
allow the rational design of new proteins with
novel properties.[82]

Proteins in various cellular compartments and

Proteomics structures tagged with green fluorescent protein (here,
white)
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,[83] which allows the separation of many proteins, mass spectrometry,[84] 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 the various
proteins present in a cell, and two-hybrid screening, which allows the systematic exploration of
protein–protein interactions.[85] The total complement of biologically possible such interactions is
known as the interactome.[86] A systematic attempt to determine the structures of proteins
representing every possible fold is known as structural genomics.[87]

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 and how it can be affected, i.e. in
drug design. As proteins are too small to be seen under a light microscope, other methods have to be
employed to determine their structure. Common experimental methods include X-ray crystallography
and NMR spectroscopy, both of which can produce structural 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
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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;[41]: 340–41 a variant known as electron crystallography can produce high-resolution
information in some cases, especially for two-dimensional crystals of membrane proteins.[88] 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.[89]

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 and
large protein complexes, by contrast, are difficult to crystallize and are underrepresented in the
PDB.[90] 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.[91]

Structure prediction
Complementary to the field of structural
genomics, protein structure prediction
develops efficient mathematical models
of proteins to computationally predict
the molecular formations in theory,
instead of detecting structures with
laboratory observation.[92] 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.[93] Although producing
accurate models remains a challenge
when only distantly related template Constituent amino-acids can be analyzed to predict secondary,
structures are available, it has been tertiary and quaternary protein structure, in this case hemoglobin
suggested that sequence alignment is the containing heme units.
bottleneck in this process, as quite
accurate models can be produced if a
"perfect" sequence alignment is known.[94] Many structure prediction methods have served to inform
the emerging field of protein engineering, in which novel protein folds have already been designed.[95]

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Many proteins (in eukaryotes ~33%) contain large unstructured but biologically functional segments
and can be classified as intrinsically disordered proteins. Predicting and analysing protein disorder is
an important part of protein structure characterisation.[96]

In silico simulation of dynamical processes

A more complex computational problem is the prediction of intermolecular interactions, such as in
molecular docking,[97] protein folding, protein–protein interaction and chemical reactivity.
Mathematical models to simulate these dynamical processes involve molecular mechanics, in
particular, molecular dynamics. In this regard, in silico simulations discovered the folding of small α-
helical protein domains such as the villin headpiece,[98] the HIV accessory protein[99] and hybrid
methods combining standard molecular dynamics with quantum mechanical mathematics have
explored the electronic states of rhodopsins.[100]

Beyond classical molecular dynamics, quantum dynamics methods allow the simulation of proteins in
atomistic detail with an accurate description of quantum mechanical effects. Examples include the
multi-layer multi-configuration time-dependent Hartree method and the hierarchical equations of
motion approach, which have been applied to plant cryptochromes[101] and bacteria light-harvesting
complexes,[102] respectively. Both quantum and classical mechanical simulations of biological-scale
systems are extremely computationally demanding, so distributed computing initiatives such as the
Folding@home project facilitate the molecular modeling by exploiting advances in GPU parallel
processing and Monte Carlo techniques.[103][104]

Chemical analysis
The total nitrogen content of organic matter is mainly formed by the amino groups in proteins. The
total Kjeldahl nitrogen (TKN) is a measure of nitrogen widely used in the analysis of (waste) water,
soil, food, feed and organic matter in general. As the name suggests, the Kjeldahl method is applied.
More sensitive methods are available.[105][106]

Digestion
In the absence of catalysts, proteins are slow to hydrolyze.[107]
The breakdown of proteins to small peptides and amino acids
(proteolysis) is a step in digestion; these breakdown products are
then absorbed in the small intestine.[108] The hydrolysis of
proteins relies on enzymes called proteases or peptidases.
Proteases, which are themselves proteins, come in several types
according to the particular peptide bonds that they cleave as well
as their tendency to cleave peptide bonds at the terminus of a Hydrolysis of protein. X = HCl and
protein (exopeptidases) vs peptide bonds at the interior of the heat for industrial proteolysis. X =
protein (endopeptidases).[109] Pepsin is an endopeptidase in the protease for biological proteolysis
stomach. Subsequent to the stomach, the pancreas secretes other
proteases to complete the hydrolysis, these include trypsin and
chymotrypsin.[110]
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Protein hydrolysis is employed commercially as a means of producing amino acids from bulk sources
of protein, such as blood meal, feathers, keratin. Such materials are treated with hot hydrochloric
acid, which effects the hydrolysis of the peptide bonds.[111]

Mechanical properties
The mechanical properties of proteins are highly diverse and are often central to their biological
function, as in the case of proteins like keratin and collagen.[112] For instance, the ability of muscle
tissue to continually expand and contract is directly tied to the elastic properties of their underlying
protein makeup.[113][114] Beyond fibrous proteins, the conformational dynamics of enzymes[115] and
the structure of biological membranes, among other biological functions, are governed by the
mechanical properties of the proteins. Outside of their biological context, the unique mechanical
properties of many proteins, along with their relative sustainability when compared to synthetic
polymers, have made them desirable targets for next-generation materials design.[116][117]

Young's modulus, E, is calculated as the axial stress σ over the resulting strain ε. It is a measure of the
relative stiffness of a material. In the context of proteins, this stiffness often directly correlates to
biological function. For example, collagen, found in connective tissue, bones, and cartilage, and
keratin, found in nails, claws, and hair, have observed stiffnesses that are several orders of magnitude
higher than that of elastin,[118] which is thought to give elasticity to structures such as blood vessels,
pulmonary tissue, and bladder tissue, among others.[119][120] In comparison to this, globular proteins,
such as Bovine Serum Albumin, which float relatively freely in the cytosol and often function as
enzymes (and thus undergoing frequent conformational changes) have comparably much lower
Young's moduli.[121][122]

The Young's modulus of a single protein can be found through molecular dynamics simulation. Using
either atomistic force-fields, such as CHARMM or GROMOS, or coarse-grained forcefields like
Martini,[123] a single protein molecule can be stretched by a uniaxial force while the resulting
extension is recorded in order to calculate the strain.[124][125] Experimentally, methods such as atomic
force microscopy can be used to obtain similar data.[126] The internal dynamics of proteins involve
subtle elastic and plastic deformations induced by viscoelastic forces, which can be probed by nano-
rheology techniques.[127]

At the macroscopic level, the Young's modulus of cross-linked protein networks can be obtained
through more traditional mechanical testing. Experimentally observed values for a few proteins can
be seen below.

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Elasticity of various proteins

Protein Protein class Young's modulus

keratin (cross-linked) fibrous 1.5–10 GPa[128]

elastin (cross-linked) fibrous 1 MPa[118]

fibrin (cross-linked) fibrous 1–10 MPa[118]

collagen (cross-linked) fibrous 5–7.5 GPa[118][129]

resilin (cross-linked) fibrous 1–2 MPa[118]

bovine serum albumin (cross-linked) globular 2.5–15 kPa[121]

β-barrel outer membrane proteins membrane 20–45 GPa[130]

See also
Deproteination – Technique in research of live materials
DNA-binding protein – Proteins that bind with DNA
Index of protein-related articles
Intein
List of proteins
Macromolecule – Very large molecule
Protein evolution – Study of changes in DNA and RNA over time
Protein sequence space – Representation of possible genetic sequences
Protein superfamily – Grouping of proteins
Protein toxicity – Buildup of metabolic waste due to kidney dysfunction
Proteopathy – Diseases caused by abnormal protein structure
Proteopedia – 3D encyclopedia of proteins and other molecules

References
1. Osborne TB (1909). "History" ([Link] The
Vegetable Proteins. pp. 1–6.
2. Reynolds JA, Tanford C (2003). Nature's Robots: A History of Proteins (Oxford Paperbacks). New
York, New York: Oxford University Press. p. 15. ISBN 978-0-19-860694-9.
3. Tanford C (2001). Nature's robots: a history of proteins ([Link]
0000tanf). Internet Archive. Oxford; Toronto: Oxford University Press. ISBN 978-0-19-850466-5.
4. Mulder GJ (1838). "Sur la composition de quelques substances animales" ([Link]
am/bulletindesscien00leyd#page/104/mode/2up). Bulletin des Sciences Physiques et Naturelles
en Néerlande: 104.
5. Hartley H (August 1951). "Origin of the word 'protein' " ([Link]
Nature. 168 (4267): 244. Bibcode:1951Natur.168..244H ([Link]
atur.168..244H). doi:10.1038/168244a0 ([Link] PMID 14875059
([Link] S2CID 4271525 ([Link]
pusID:4271525).

[Link] 17/30
8/3/26, 3:32 PM Protein - Wikipedia

6. Perrett D (August 2007). "From 'protein' to the beginnings of clinical proteomics". Proteomics.
Clinical Applications. 1 (8): 720–738. doi:10.1002/prca.200700525 ([Link]
a.200700525). PMID 21136729 ([Link] S2CID 32843102 (ht
tps://[Link]/CorpusID:32843102).
7. "Protein, N". Protein (n.). Oxford English Dictionary. July 2023. doi:10.1093/OED/5657543824 (htt
ps://[Link]/10.1093%2FOED%2F5657543824).
8. Bischoff TL, Voit C (1860). Die Gesetze der Ernaehrung des Pflanzenfressers durch neue
Untersuchungen festgestellt (in German). Leipzig, Heidelberg: C.F. Winter'sche Verlagshandlung.
9. Osborne TB (April 1913). "In Memoriam Heinrich Ritthausen" ([Link]
a/blumenzeitung09hssl#page/400/mode/2up). Biochemical Bulletin. II (7). Columbia University
Biochemical Association: 338. Retrieved 1 January 2016., archived at the Biodiversity Heritage
Library
10. Simoni RD, Hill RL, Vaughan M (2002-05-03). "Nutritional Biochemistry and the Amino Acid
Composition of Proteins: The early years of protein chemistry, the Work of Thomas B. Osborne
and Lafayette B. Mendel" ([Link] Journal of
Biological Chemistry. 277 (18): 14–15. doi:10.1016/S0021-9258(19)35800-4 ([Link]
16%2FS0021-9258%2819%2935800-4).
11. Osborne TB, Mendel LB, Ferry EL, Wakeman AJ (1916). "The Amino-Acid Minimum for
Maintenance and Growth, as Exemplified by Further Experiments with Lysine and Tryptophane" (h
ttps://[Link]/10.1016%2FS0021-9258%2818%2987509-3). Journal of Biological Chemistry. 25
(1): 1–12. doi:10.1016/S0021-9258(18)87509-3 ([Link]
2987509-3).
12. Simoni RD, Hill RL, Vaughan M (2002-09-13). "The Discovery of the Amino Acid Threonine: the
Work of William C. Rose" ([Link] Journal of
Biological Chemistry. 277 (37): 56–58. doi:10.1016/S0021-9258(20)74369-3 ([Link]
16%2FS0021-9258%2820%2974369-3).
13. "Hofmeister, Franz" ([Link]
press-releases/hofmeister-franz). [Link]. Archived ([Link]
405073423/[Link]
eases/hofmeister-franz) from the original on 5 April 2017. Retrieved 4 April 2017.
14. Koshland DE, Haurowitz F. "Protein, section: Classification of protein" ([Link]
science/protein/Conformation-of-proteins-in-interfaces#ref593795). [Link]. Archived (http
s://[Link]/web/20170404225132/[Link]
on-of-proteins-in-interfaces#ref593795) from the original on 4 April 2017. Retrieved 4 April 2017.
15. Sumner JB (August 1926). "The Isolation and Crystallization of the Enzyme Urease" ([Link]
g/10.1016%2FS0021-9258%2818%2984560-4). Journal of Biological Chemistry. 69 (2): 435–441.
Bibcode:1926JBiCh..69..435S ([Link]
doi:10.1016/S0021-9258(18)84560-4 ([Link]
4).
16. Pauling L, Corey RB (May 1951). "Atomic coordinates and structure factors for two helical
configurations of polypeptide chains" ([Link]
Proceedings of the National Academy of Sciences of the United States of America. 37 (5): 235–
240. Bibcode:1951PNAS...37..235P ([Link]
doi:10.1073/pnas.37.5.235 ([Link] PMC 1063348 ([Link]
[Link]/pmc/articles/PMC1063348). PMID 14834145 ([Link]
14834145).
17. Kauzmann W (May 1956). "Structural factors in protein denaturation". Journal of Cellular
Physiology. Supplement. 47 (Suppl 1): 113–131. doi:10.1002/jcp.1030470410 ([Link]
002%2Fjcp.1030470410). PMID 13332017 ([Link]

[Link] 18/30
8/3/26, 3:32 PM Protein - Wikipedia

18. Kauzmann W (1959). "Some Factors in the Interpretation of Protein Denaturation". In Anfinsen Jr
C, Anson M, Bailey K, Edsall JT (eds.). Advances in Protein Chemistry ([Link]
com/retrieve/pii/S0065323308606087). Vol. 14. Elsevier. pp. 1–63. doi:10.1016/s0065-
3233(08)60608-7 ([Link] ISBN 978-0-12-
034214-3. PMID 14404936 ([Link] Retrieved 2025-04-21.
19. Kalman SM, Linderstrøm-Lang K, Ottesen M, Richards FM (February 1955). "Degradation of
ribonuclease by subtilisin". Biochimica et Biophysica Acta. 16 (2): 297–299. doi:10.1016/0006-
3002(55)90224-9 ([Link] PMID 14363272 (ht
tps://[Link]/14363272).
20. Dill KA (1990). "Dominant forces in protein folding" ([Link]
001). Biochemistry. 29 (31): 7133–7155. doi:10.1021/bi00483a001 ([Link]
0483a001). PMID 2207096 ([Link]
21. Sanger F (1949). "The terminal peptides of insulin" ([Link]
C1275055). The Biochemical Journal. 45 (5): 563–574. doi:10.1042/bj0450563 ([Link]
1042%2Fbj0450563). PMC 1275055 ([Link]
PMID 15396627 ([Link]
22. Sanger F. (1958), Nobel lecture: The chemistry of insulin ([Link]
stry/laureates/1958/[Link]) (PDF), [Link], archived ([Link]
eb/20130319022148/[Link]
[Link]) (PDF) from the original on 2013-03-19, retrieved 2016-02-09
23. Richards FM (1972). "The 1972 nobel prize for chemistry". Science. 178 (4060): 492–3.
Bibcode:1972Sci...178..492R ([Link]
doi:10.1126/science.178.4060.492 ([Link]
PMID 17754377 ([Link]
24. Marshall GR, Feng JA, Kuster DJ (2008). "Back to the future: Ribonuclease A" ([Link]
002%2Fbip.20845). Biopolymers. 90 (3): 259–77. doi:10.1002/bip.20845 ([Link]
2%2Fbip.20845). PMID 17868092 ([Link]
25. Stoddart C (1 March 2022). "Structural biology: How proteins got their close-up" ([Link]
0.1146%2Fknowable-022822-1). Knowable Magazine. doi:10.1146/knowable-022822-1 ([Link]
[Link]/10.1146%2Fknowable-022822-1).
26. Muirhead H, Perutz MF (August 1963). ". Structure of haemoglobin. A three-dimensional Fourier
synthesis of reduced human haemoglobin at 5.5 Å resolution". Nature. 199 (4894): 633–638.
Bibcode:1963Natur.199..633M ([Link]
doi:10.1038/199633a0 ([Link] PMID 14074546 ([Link]
[Link]/14074546). S2CID 4257461 ([Link]
27. Kendrew JC, Bodo G, Dintzis HM, Parrish RG, Wyckoff H, Phillips DC (March 1958). "A three-
dimensional model of the myoglobin molecule obtained by x-ray analysis". Nature. 181 (4610):
662–666. Bibcode:1958Natur.181..662K ([Link]
K). doi:10.1038/181662a0 ([Link] PMID 13517261 ([Link]
[Link]/13517261). S2CID 4162786 ([Link]
6).
28. Zhou ZH (April 2008). "Towards atomic resolution structural determination by single-particle cryo-
electron microscopy" ([Link] Current Opinion
in Structural Biology. 18 (2): 218–228. doi:10.1016/[Link].2008.03.004 ([Link]
sbi.2008.03.004). PMC 2714865 ([Link]
PMID 18403197 ([Link]
29. Keskin O, Tuncbag N, Gursoy A (April 2008). "Characterization and prediction of protein interfaces
to infer protein-protein interaction networks". Current Pharmaceutical Biotechnology. 9 (2): 67–76.
doi:10.2174/138920108783955191 ([Link]
hdl:11511/32640 ([Link] PMID 18393863 ([Link]
[Link]/18393863).

[Link] 19/30
8/3/26, 3:32 PM Protein - Wikipedia

30. "Summary Statistics" ([Link] RCSB PDB. Retrieved 2024-04-20.

31. McDonald AG, Tipton KF (2023). "Enzyme nomenclature and classification: the state of the art" (ht
tps://[Link]/10.1111%2Ffebs.16274). The FEBS Journal. 290 (9): 2214–2231.
doi:10.1111/febs.16274 ([Link] ISSN 1742-464X ([Link]
[Link]/issn/1742-464X). PMID 34773359 ([Link]
32. The Gene Ontology Consortium (January 2008). "The Gene Ontology project in 2008" ([Link]
[Link]/pmc/articles/PMC2238979). Nucleic Acids Research. 36 (Database issue):
D440–4. doi:10.1093/nar/gkm883 ([Link] PMC 2238979 (ht
tps://[Link]/pmc/articles/PMC2238979). PMID 17984083 ([Link]
[Link]/17984083).
33. Ekman D, Björklund AK, Frey-Skött J, Elofsson A (April 2005). "Multi-domain proteins in the three
kingdoms of life: orphan domains and other unassigned regions". Journal of Molecular Biology.
348 (1): 231–243. Bibcode:2005JMBio.348..231E ([Link]
48..231E). doi:10.1016/[Link].2005.02.007 ([Link]
PMID 15808866 ([Link]
34. Nelson DL, Cox MM (2005). Lehninger's Principles of Biochemistry (4th ed.). New York, New York:
W. H. Freeman and Company. Bibcode:[Link].....N ([Link]
[Link].....N).
35. Gutteridge A, Thornton JM (November 2005). "Understanding nature's catalytic toolkit". Trends in
Biochemical Sciences. 30 (11): 622–629. doi:10.1016/[Link].2005.09.006 ([Link]
[Link].2005.09.006). PMID 16214343 ([Link]
36. Murray RF, Harper HW, Granner DK, Mayes PA, Rodwell VW (2006). Harper's Illustrated
Biochemistry. New York: Lange Medical Books/McGraw-Hill. ISBN 978-0-07-146197-9.
37. Reusch W (5 May 2013). "Peptides & Proteins" ([Link]
rttxtjml/[Link]). Michigan State University Department of Chemistry.
38. Stryer L (2002). Biochemistry (Fifth ed.). W. H. Freeman and Company. p. 826. ISBN 0-7167-
4684-0.
39. Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, et al. (2004). Molecular Cell
Biology (5th ed.). New York, New York: WH Freeman and Company.
40. Ardejani MS, Powers ET, Kelly JW (August 2017). "Using Cooperatively Folded Peptides To
Measure Interaction Energies and Conformational Propensities" ([Link]
c/articles/PMC5584629). Accounts of Chemical Research. 50 (8): 1875–1882.
doi:10.1021/[Link].7b00195 ([Link]
PMC 5584629 ([Link] PMID 28723063 (https://
[Link]/28723063).
41. Branden C, Tooze J (1999). Introduction to Protein Structure. New York: Garland Pub. ISBN 978-
0-8153-2305-1.
42. Van Holde KE, Mathews CK (1996). Biochemistry ([Link]
Menlo Park, California: Benjamin/Cummings. ISBN 978-0-8053-3931-4.
43. Milo R (December 2013). "What is the total number of protein molecules per cell volume? A call to
rethink some published values" ([Link]
BioEssays. 35 (12): 1050–1055. doi:10.1002/bies.201300066 ([Link]
1300066). PMC 3910158 ([Link]
PMID 24114984 ([Link]
44. Beck M, Schmidt A, Malmstroem J, Claassen M, Ori A, Szymborska A, et al. (November 2011).
"The quantitative proteome of a human cell line" ([Link]
261713). Molecular Systems Biology. 7 549. doi:10.1038/msb.2011.82 ([Link]
Fmsb.2011.82). PMC 3261713 ([Link]
PMID 22068332 ([Link]

[Link] 20/30
8/3/26, 3:32 PM Protein - Wikipedia

45. Wu L, Candille SI, Choi Y, Xie D, Jiang L, Li-Pook-Than J, et al. (July 2013). "Variation and genetic
control of protein abundance in humans" ([Link]
1). Nature. 499 (7456): 79–82. Bibcode:2013Natur.499...79W ([Link]
013Natur.499...79W). doi:10.1038/nature12223 ([Link]
PMC 3789121 ([Link] PMID 23676674 (https://
[Link]/23676674).
46. Ellis R (1979). "The most abundant protein in the world". Trends in Biochemical Sciences. 4 (11):
241–244. doi:10.1016/0968-0004(79)90212-3 ([Link]
0212-3).
47. Dobson CM (2000). "The nature and significance of protein folding". In Pain RH (ed.).
Mechanisms of Protein Folding. Oxford, Oxfordshire: Oxford University Press. pp. 1–28.
ISBN 978-0-19-963789-8.
48. Kozlowski LP (January 2017). "Proteome-pI: proteome isoelectric point database" ([Link]
[Link]/pmc/articles/PMC5210655). Nucleic Acids Research. 45 (D1): D1112–D1116.
doi:10.1093/nar/gkw978 ([Link] PMC 5210655 ([Link]
[Link]/pmc/articles/PMC5210655). PMID 27789699 ([Link]
27789699).
49. Fulton AB, Isaacs WB (April 1991). "Titin, a huge, elastic sarcomeric protein with a probable role in
morphogenesis". BioEssays. 13 (4): 157–161. doi:10.1002/bies.950130403 ([Link]
2%2Fbies.950130403). PMID 1859393 ([Link]
S2CID 20237314 ([Link]
50. Bruckdorfer T, Marder O, Albericio F (February 2004). "From production of peptides in milligram
amounts for research to multi-tons quantities for drugs of the future". Current Pharmaceutical
Biotechnology. 5 (1): 29–43. doi:10.2174/1389201043489620 ([Link]
1043489620). PMID 14965208 ([Link]
51. Ovaa H, Wals K (2014-04-01). "Unnatural amino acid incorporation in E. coli: current and future
applications in the design of therapeutic proteins" ([Link]
3982533). Frontiers in Chemistry. 2: 15. Bibcode:2014FrCh....2...15O ([Link]
du/abs/2014FrCh....2...15O). doi:10.3389/fchem.2014.00015 ([Link]
014.00015). ISSN 2296-2646 ([Link] PMC 3982533 (https://
[Link]/pmc/articles/PMC3982533). PMID 24790983 ([Link]
ov/24790983).
52. Schwarzer D, Cole PA (December 2005). "Protein semisynthesis and expressed protein ligation:
chasing a protein's tail". Current Opinion in Chemical Biology. 9 (6): 561–569.
doi:10.1016/[Link].2005.09.018 ([Link] PMID 16226484
([Link]
53. Kent SB (February 2009). "Total chemical synthesis of proteins". Chemical Society Reviews. 38
(2): 338–351. Bibcode:2009CSRev..38..338K ([Link]
338K). doi:10.1039/b700141j ([Link] PMID 19169452 ([Link]
[Link]/19169452). S2CID 5432012 ([Link]
012).
54. Fernández A, Scott R (September 2003). "Dehydron: a structurally encoded signal for protein
interaction" ([Link] Biophysical Journal. 85 (3):
1914–1928. Bibcode:2003BpJ....85.1914F ([Link]
F). doi:10.1016/S0006-3495(03)74619-0 ([Link]
9-0). PMC 1303363 ([Link] PMID 12944304 (h
ttps://[Link]/12944304).
55. Garrett R, Grisham CM (2010). Biochemistry (4th ed.). Belmont, CA: Brooks/Cole, Cengage
Learning. ISBN 978-0-495-10935-8.

[Link] 21/30
8/3/26, 3:32 PM Protein - Wikipedia

56. Drees F, Gertler FB (2008-02-01). "Ena/VASP: proteins at the tip of the nervous system" ([Link]
[Link]/pmc/articles/PMC2515615). Current Opinion in Neurobiology. Development.
18 (1): 53–59. doi:10.1016/[Link].2008.05.007 ([Link]
PMC 2515615 ([Link] PMID 18508258 (https://
[Link]/18508258).
57. Davey NE, Van Roey K, Weatheritt RJ, Toedt G, Uyar B, Altenberg B, et al. (January 2012).
"Attributes of short linear motifs". Molecular BioSystems. 8 (1): 268–281.
doi:10.1039/c1mb05231d ([Link] PMID 21909575 ([Link]
[Link]/21909575).
58. Kumar M, Gouw M, Michael S, Sámano-Sánchez H, Pancsa R, Glavina J, et al. (2020-01-08).
"ELM-the eukaryotic linear motif resource in 2020" ([Link]
C7145657). Nucleic Acids Research. 48 (D1): D296–D306. doi:10.1093/nar/gkz1030 ([Link]
rg/10.1093%2Fnar%2Fgkz1030). PMC 7145657 ([Link]
145657). PMID 31680160 ([Link]
59. Voet D, Voet JG. (2004). Biochemistry Vol 1 3rd ed. Wiley: Hoboken, NJ.
60. Sankaranarayanan R, Moras D (2001). "The fidelity of the translation of the genetic code" (https://
[Link]/10.18388%2Fabp.2001_3918). Acta Biochimica Polonica. 48 (2): 323–335.
doi:10.18388/abp.2001_3918 ([Link] PMID 11732604 (http
s://[Link]/11732604).
61. Copland JA, Sheffield-Moore M, Koldzic-Zivanovic N, Gentry S, Lamprou G, Tzortzatou-
Stathopoulou F, et al. (June 2009). "Sex steroid receptors in skeletal differentiation and epithelial
neoplasia: is tissue-specific intervention possible?". BioEssays. 31 (6): 629–641.
doi:10.1002/bies.200800138 ([Link] PMID 19382224 (http
s://[Link]/19382224). S2CID 205469320 ([Link]
sID:205469320).
62. Samarin S, Nusrat A (January 2009). "Regulation of epithelial apical junctional complex by Rho
family GTPases" ([Link] Frontiers in Bioscience. 14 (3): 1129–1142.
doi:10.2741/3298 ([Link] PMID 19273120 ([Link]
[Link]/19273120).
63. Bairoch A (January 2000). "The ENZYME database in 2000" ([Link]
icles/PMC102465). Nucleic Acids Research. 28 (1): 304–305. doi:10.1093/nar/28.1.304 ([Link]
[Link]/10.1093%2Fnar%2F28.1.304). PMC 102465 ([Link]
102465). PMID 10592255 ([Link]
64. Radzicka A, Wolfenden R (January 1995). "A proficient enzyme". Science. 267 (5194): 90–93.
Bibcode:1995Sci...267...90R ([Link]
doi:10.1126/science.7809611 ([Link] PMID 7809611 (http
s://[Link]/7809611).
65. EBI External Services (2010-01-20). "The Catalytic Site Atlas at The European Bioinformatics
Institute" ([Link] [Link]. Archived ([Link]
[Link]/web/20130803032349/[Link] from the
original on 2013-08-03. Retrieved 2011-01-16.
66. Pickel B, Schaller A (October 2013). "Dirigent proteins: molecular characteristics and potential
biotechnological applications". Applied Microbiology and Biotechnology. 97 (19): 8427–8438.
doi:10.1007/s00253-013-5167-4 ([Link]
PMID 23989917 ([Link] S2CID 1896003 ([Link]
[Link]/CorpusID:1896003).
67. Rüdiger H, Siebert HC, Solís D, Jiménez-Barbero J, Romero A, von der Lieth CW, et al. (April
2000). "Medicinal chemistry based on the sugar code: fundamentals of lectinology and
experimental strategies with lectins as targets". Current Medicinal Chemistry. 7 (4): 389–416.
doi:10.2174/0929867003375164 ([Link]
PMID 10702616 ([Link]

[Link] 22/30
8/3/26, 3:32 PM Protein - Wikipedia

68. Cooper GM (2000). "Signaling Molecules and Their Receptors". The Cell: A Molecular Approach
([Link] (2nd ed.). Sunderland, Massachusetts: Sinauer
Associates.
69. "Experimental Animal and In Vitro Study Designs" ([Link]
1/), Evaluating Chemical and Other Agent Exposures for Reproductive and Developmental
Toxicity, National Academies Press, 2001, retrieved 2024-12-23
70. Ricard J, Cornish-Bowden A (July 1987). "Co-operative and allosteric enzymes: 20 years on" (http
s://[Link]/doi/10.1111/j.1432-1033.1987.tb13510.x). European Journal of
Biochemistry. 166 (2): 255–272. doi:10.1111/j.1432-1033.1987.tb13510.x ([Link]
2Fj.1432-1033.1987.tb13510.x). PMID 3301336 ([Link]
71. Lipinski C, Hopkins A (December 2004). "Navigating chemical space for biology and medicine" (htt
ps://[Link]/articles/nature03193). Nature. 432 (7019): 855–861.
Bibcode:2004Natur.432..855L ([Link]
doi:10.1038/nature03193 ([Link] PMID 15602551 ([Link]
[Link]/15602551).
72. Danchin A, Médigue C, Gascuel O, Soldano H, Hénaut A (1991). "From data banks to data bases"
([Link] Research in Microbiology. 142
(7–8): 913–916. doi:10.1016/0923-2508(91)90073-J ([Link]
1%2990073-J). PMID 1784830 ([Link]
73. Terpe K (January 2003). "Overview of tag protein fusions: from molecular and biochemical
fundamentals to commercial systems". Applied Microbiology and Biotechnology. 60 (5): 523–533.
doi:10.1007/s00253-002-1158-6 ([Link]
PMID 12536251 ([Link] S2CID 206934268 ([Link]
[Link]/CorpusID:206934268).
74. Hey J, Posch A, Cohen A, Liu N, Harbers A (2008). "Fractionation of Complex Protein Mixtures by
Liquid-Phase Isoelectric Focusing". 2D PAGE: Sample Preparation and Fractionation. Methods in
Molecular Biology. Vol. 424. pp. 225–239. doi:10.1007/978-1-60327-064-9_19 ([Link]
007%2F978-1-60327-064-9_19). ISBN 978-1-58829-722-8. PMID 18369866 ([Link]
[Link]/18369866).
75. Stepanenko OV, Verkhusha VV, Kuznetsova IM, Uversky VN, Turoverov KK (August 2008).
"Fluorescent proteins as biomarkers and biosensors: throwing color lights on molecular and
cellular processes" ([Link] Current Protein &
Peptide Science. 9 (4): 338–369. doi:10.2174/138920308785132668 ([Link]
138920308785132668). PMC 2904242 ([Link]
PMID 18691124 ([Link]
76. Yuste R (December 2005). "Fluorescence microscopy today". Nature Methods. 2 (12): 902–904.
Bibcode:2005NatCB...2..902Y ([Link]
doi:10.1038/nmeth1205-902 ([Link] PMID 16299474 (http
s://[Link]/16299474). S2CID 205418407 ([Link]
sID:205418407).
77. Margolin W (January 2000). "Green fluorescent protein as a reporter for macromolecular
localization in bacterial cells". Methods. 20 (1): 62–72. doi:10.1006/meth.1999.0906 ([Link]
g/10.1006%2Fmeth.1999.0906). PMID 10610805 ([Link]
78. Hrycaj S (17 October 2023). "Immunohistochemistry: Origins, Tips, and a Look to the Future" (http
s://[Link]/immunohistochemistry-origins-tips-and-a-look-to-the-future-71439). The
Scientist Magazine. Retrieved 2024-12-22.
79. Walker JH, Wilson K (2000). Principles and Techniques of Practical Biochemistry. Cambridge, UK:
Cambridge University Press. pp. 287–89. ISBN 978-0-521-65873-7.

[Link] 23/30
8/3/26, 3:32 PM Protein - Wikipedia

80. Mayhew TM, Lucocq JM (August 2008). "Developments in cell biology for quantitative
immunoelectron microscopy based on thin sections: a review" ([Link]
articles/PMC2491712). Histochemistry and Cell Biology. 130 (2) 299: 299–313.
doi:10.1007/s00418-008-0451-6 ([Link] PMC 2491712
([Link] PMID 18553098 ([Link]
[Link]/18553098).
81. Hohsaka T, Sisido M (December 2002). "Incorporation of non-natural amino acids into proteins".
Current Opinion in Chemical Biology. 6 (6): 809–815. doi:10.1016/S1367-5931(02)00376-9 (http
s://[Link]/10.1016%2FS1367-5931%2802%2900376-9). PMID 12470735 ([Link]
[Link]/12470735).
82. Cedrone F, Ménez A, Quéméneur E (August 2000). "Tailoring new enzyme functions by rational
redesign". Current Opinion in Structural Biology. 10 (4): 405–410. doi:10.1016/S0959-
440X(00)00106-8 ([Link] PMID 10981626
([Link]
83. Görg A, Weiss W, Dunn MJ (December 2004). "Current two-dimensional electrophoresis
technology for proteomics". Proteomics. 4 (12): 3665–3685. doi:10.1002/pmic.200401031 (https://
[Link]/10.1002%2Fpmic.200401031). PMID 15543535 ([Link]
5). S2CID 28594824 ([Link]
84. Conrotto P, Souchelnytskyi S (September 2008). "Proteomic approaches in biological and medical
sciences: principles and applications". Experimental Oncology. 30 (3): 171–180. PMID 18806738
([Link]
85. Koegl M, Uetz P (December 2007). "Improving yeast two-hybrid screening systems". Briefings in
Functional Genomics & Proteomics. 6 (4): 302–312. doi:10.1093/bfgp/elm035 ([Link]
093%2Fbfgp%2Felm035). PMID 18218650 ([Link]
86. Plewczyński D, Ginalski K (2009). "The interactome: predicting the protein-protein interactions in
cells" ([Link] Cellular & Molecular Biology
Letters. 14 (1): 1–22. doi:10.2478/s11658-008-0024-7 ([Link]
24-7). PMC 6275871 ([Link] PMID 18839074
([Link]
87. Zhang C, Kim SH (February 2003). "Overview of structural genomics: from structure to function"
([Link] Current Opinion in Chemical Biology. 7 (1): 28–32.
doi:10.1016/S1367-5931(02)00015-7 ([Link]
7). PMID 12547423 ([Link]
88. Gonen T, Cheng Y, Sliz P, Hiroaki Y, Fujiyoshi Y, Harrison SC, et al. (December 2005). "Lipid-
protein interactions in double-layered two-dimensional AQP0 crystals" ([Link]
ov/pmc/articles/PMC1350984). Nature. 438 (7068): 633–638. Bibcode:2005Natur.438..633G (http
s://[Link]/abs/2005Natur.438..633G). doi:10.1038/nature04321 ([Link]
1038%2Fnature04321). PMC 1350984 ([Link]
PMID 16319884 ([Link]
89. Standley DM, Kinjo AR, Kinoshita K, Nakamura H (July 2008). "Protein structure databases with
new web services for structural biology and biomedical research" ([Link]
b%2Fbbn015). Briefings in Bioinformatics. 9 (4): 276–285. doi:10.1093/bib/bbn015 ([Link]
10.1093%2Fbib%2Fbbn015). PMID 18430752 ([Link]
90. Walian P, Cross TA, Jap BK (2004). "Structural genomics of membrane proteins" ([Link]
[Link]/pmc/articles/PMC395774). Genome Biology. 5 (4): 215. doi:10.1186/gb-2004-5-4-
215 ([Link] PMC 395774 ([Link]
c/articles/PMC395774). PMID 15059248 ([Link]
91. Sleator RD (2012). "Prediction of Protein Functions". Functional Genomics. Methods in Molecular
Biology. Vol. 815. pp. 15–24. doi:10.1007/978-1-61779-424-7_2 ([Link]
-61779-424-7_2). ISBN 978-1-61779-423-0. PMID 22130980 ([Link]
130980).

[Link] 24/30
8/3/26, 3:32 PM Protein - Wikipedia

92. Zhang Y (June 2008). "Progress and challenges in protein structure prediction" ([Link]
[Link]/pmc/articles/PMC2680823). Current Opinion in Structural Biology. 18 (3): 342–348.
doi:10.1016/[Link].2008.02.004 ([Link] PMC 2680823 (http
s://[Link]/pmc/articles/PMC2680823). PMID 18436442 ([Link]
[Link]/18436442).
93. Xiang Z (June 2006). "Advances in homology protein structure modeling" ([Link]
[Link]/pmc/articles/PMC1839925). Current Protein & Peptide Science. 7 (3): 217–227.
doi:10.2174/138920306777452312 ([Link]
PMC 1839925 ([Link] PMID 16787261 (https://
[Link]/16787261).
94. Zhang Y, Skolnick J (January 2005). "The protein structure prediction problem could be solved
using the current PDB library" ([Link]
Proceedings of the National Academy of Sciences of the United States of America. 102 (4): 1029–
1034. Bibcode:2005PNAS..102.1029Z ([Link]
Z). doi:10.1073/pnas.0407152101 ([Link] PMC 545829
([Link] PMID 15653774 ([Link]
[Link]/15653774).
95. Kuhlman B, Dantas G, Ireton GC, Varani G, Stoddard BL, Baker D (November 2003). "Design of a
novel globular protein fold with atomic-level accuracy". Science. 302 (5649): 1364–1368.
Bibcode:2003Sci...302.1364K ([Link]
doi:10.1126/science.1089427 ([Link] PMID 14631033 (htt
ps://[Link]/14631033). S2CID 1939390 ([Link]
ID:1939390).
96. Ward JJ, Sodhi JS, McGuffin LJ, Buxton BF, Jones DT (March 2004). "Prediction and functional
analysis of native disorder in proteins from the three kingdoms of life". Journal of Molecular
Biology. 337 (3): 635–645. Bibcode:2004JMBio.337..635W ([Link]
4JMBio.337..635W). CiteSeerX [Link].5605 ([Link]
doi=[Link].5605). doi:10.1016/[Link].2004.02.002 ([Link]
02). PMID 15019783 ([Link]
97. Ritchie DW (February 2008). "Recent progress and future directions in protein-protein docking".
Current Protein & Peptide Science. 9 (1): 1–15. CiteSeerX [Link].4946 ([Link]
[Link]/viewdoc/summary?doi=[Link].4946). doi:10.2174/138920308783565741 ([Link]
g/10.2174%2F138920308783565741). PMID 18336319 ([Link]
19).
98. Zagrovic B, Snow CD, Shirts MR, Pande VS (November 2002). "Simulation of folding of a small
alpha-helical protein in atomistic detail using worldwide-distributed computing". Journal of
Molecular Biology. 323 (5): 927–937. Bibcode:2002JMBio.323..927Z ([Link]
u/abs/2002JMBio.323..927Z). CiteSeerX [Link].8664 ([Link]
mmary?doi=[Link].8664). doi:10.1016/S0022-2836(02)00997-X ([Link]
0022-2836%2802%2900997-X). PMID 12417204 ([Link]
99. Herges T, Wenzel W (January 2005). "In silico folding of a three helix protein and characterization
of its free-energy landscape in an all-atom force field". Physical Review Letters. 94 (1) 018101.
arXiv:physics/0310146 ([Link] Bibcode:2005PhRvL..94a8101H (h
ttps://[Link]/abs/2005PhRvL..94a8101H). doi:10.1103/PhysRevLett.94.018101 (ht
tps://[Link]/10.1103%2FPhysRevLett.94.018101). PMID 15698135 ([Link]
gov/15698135). S2CID 1477100 ([Link]
100. Hoffmann M, Wanko M, Strodel P, König PH, Frauenheim T, Schulten K, et al. (August 2006).
"Color tuning in rhodopsins: the mechanism for the spectral shift between bacteriorhodopsin and
sensory rhodopsin II". Journal of the American Chemical Society. 128 (33): 10808–10818.
Bibcode:2006JAChS.12810808H ([Link]
doi:10.1021/ja062082i ([Link] PMID 16910676 ([Link]
[Link]/16910676).
[Link] 25/30
8/3/26, 3:32 PM Protein - Wikipedia

101. Mendive-Tapia D, Mangaud E, Firmino T, de la Lande A, Desouter-Lecomte M, Meyer HD, et al.

(January 2018). "Multidimensional Quantum Mechanical Modeling of Electron Transfer and
Electronic Coherence in Plant Cryptochromes: The Role of Initial Bath Conditions". The Journal of
Physical Chemistry B. 122 (1): 126–136. Bibcode:2018JPCB..122..126M ([Link]
[Link]/abs/2018JPCB..122..126M). doi:10.1021/[Link].7b10412 ([Link]
jpcb.7b10412). PMID 29216421 ([Link]
102. Strümpfer J, Schulten K (August 2012). "Open Quantum Dynamics Calculations with the
Hierarchy Equations of Motion on Parallel Computers" ([Link]
PMC3480185). Journal of Chemical Theory and Computation. 8 (8): 2808–2816.
Bibcode:2012JCTC....8.2808S ([Link]
doi:10.1021/ct3003833 ([Link] PMC 3480185 ([Link]
[Link]/pmc/articles/PMC3480185). PMID 23105920 ([Link]
20).
103. Scheraga HA, Khalili M, Liwo A (2007). "Protein-folding dynamics: overview of molecular
simulation techniques". Annual Review of Physical Chemistry. 58: 57–83.
Bibcode:2007ARPC...58...57S ([Link]
doi:10.1146/[Link].58.032806.104614 ([Link]
m.58.032806.104614). PMID 17034338 ([Link]
104. Zheng S, Javidpour L, Sahimi M, Shing KS, Nakano A (2020). "sDMD: An open source program
for discontinuous molecular dynamics simulation of protein folding and aggregation". Computer
Physics Communications. 247 106873. Bibcode:2020CoPhC.24706873Z ([Link]
[Link]/abs/2020CoPhC.24706873Z). doi:10.1016/[Link].2019.106873 ([Link]
cpc.2019.106873).
105. Muñoz-Huerta RF, Guevara-Gonzalez RG, Contreras-Medina LM, Torres-Pacheco I, Prado-
Olivarez J, Ocampo-Velazquez RV (August 2013). "A review of methods for sensing the nitrogen
status in plants: advantages, disadvantages and recent advances" ([Link]
mc/articles/PMC3812630). Sensors. 13 (8): 10823–10843. Bibcode:2013Senso..1310823M (http
s://[Link]/abs/2013Senso..1310823M). doi:10.3390/s130810823 ([Link]
0.3390%2Fs130810823). PMC 3812630 ([Link]
0). PMID 23959242 ([Link]
106. Martin PD, Malley DF, Manning G, Fuller L (November 2002). "Determination of soil organic
carbon and nitrogen at the field level using near-infrared spectroscopy". Canadian Journal of Soil
Science. 82 (4): 413–422. Bibcode:2002CaJSS..82..413M ([Link]
2CaJSS..82..413M). doi:10.4141/S01-054 ([Link]
107. Radzicka A, Wolfenden R (1 January 1996). "Rates of Uncatalyzed Peptide Bond Hydrolysis in
Neutral Solution and the Transition State Affinities of Proteases". Journal of the American
Chemical Society. 118 (26): 6105–6109. Bibcode:1996JAChS.118.6105R ([Link]
[Link]/abs/1996JAChS.118.6105R). doi:10.1021/ja954077c ([Link]
c).
108. Keller J (2013). "Gastrointestinal Digestion and Absorption". Encyclopedia of Biological Chemistry.
Elsevier. pp. 354–359. doi:10.1016/b978-0-12-378630-2.00106-7 ([Link]
8-0-12-378630-2.00106-7). ISBN 978-0-12-378631-9.
109. Oda K (2012). "New families of carboxyl peptidases: serine-carboxyl peptidases and glutamic
peptidases" ([Link] Journal of Biochemistry. 151 (1): 13–25.
doi:10.1093/jb/mvr129 ([Link] PMID 22016395 ([Link]
[Link]/22016395).
110. Switzar L, Giera M, Niessen WM (1 March 2013). "Protein Digestion: An Overview of the Available
Techniques and Recent Developments". Journal of Proteome Research. 12 (3): 1067–1077.
doi:10.1021/pr301201x ([Link] PMID 23368288 ([Link]
[Link]/23368288).

[Link] 26/30
8/3/26, 3:32 PM Protein - Wikipedia

111. Drauz K, Grayson I, Kleemann A, Krimmer HP, Leuchtenberger W, Weckbecker C (2007). "Amino
Acids". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a02_057.pub2 (htt
ps://[Link]/10.1002%2F14356007.a02_057.pub2). ISBN 978-3-527-30385-4.
112. Gosline J, Lillie M, Carrington E, Guerette P, Ortlepp C, Savage K (February 2002). Bailey AJ,
Macmillan J, Shrewry PR, Tatham AS (eds.). "Elastic proteins: biological roles and mechanical
properties" ([Link] Philosophical Transactions
of the Royal Society of London. Series B, Biological Sciences. 357 (1418): 121–132.
doi:10.1098/rstb.2001.1022 ([Link] PMC 1692928 ([Link]
[Link]/pmc/articles/PMC1692928). PMID 11911769 ([Link]
v/11911769).
113. Maruyama K, Natori R, Nonomura Y (July 1976). "New elastic protein from muscle". Nature. 262
(5563): 58–60. Bibcode:1976Natur.262...58M ([Link]
58M). doi:10.1038/262058a0 ([Link] PMID 934326 ([Link]
[Link]/934326).
114. Tskhovrebova L, Trinick J (February 2012). "Making muscle elastic: the structural basis of
myomesin stretching" ([Link] PLOS Biology.
10 (2) e1001264. doi:10.1371/[Link].1001264 ([Link]
264). PMC 3279349 ([Link] PMID 22347814
([Link]
115. Mizraji E, Acerenza L, Lin J (November 1987). "Viscoelastic models for enzymes with multiple
conformational states". Journal of Theoretical Biology. 129 (2): 163–175.
Bibcode:1987JThBi.129..163M ([Link]
doi:10.1016/s0022-5193(87)80010-3 ([Link]
3). PMID 3455460 ([Link]
116. Schiller T, Scheibel T (2024-04-18). "Bioinspired and biomimetic protein-based fibers and their
applications" ([Link] Communications Materials. 5 (1)
56. Bibcode:2024CoMat...5...56S ([Link]
doi:10.1038/s43246-024-00488-2 ([Link]
117. Sun J, He H, Zhao K, Cheng W, Li Y, Zhang P, et al. (September 2023). "Protein fibers with self-
recoverable mechanical properties via dynamic imine chemistry" ([Link]
c/articles/PMC10475138). Nature Communications. 14 (1) 5348. Bibcode:2023NatCo..14.5348S
([Link] doi:10.1038/s41467-023-41084-1 (http
s://[Link]/10.1038%2Fs41467-023-41084-1). PMC 10475138 ([Link]
articles/PMC10475138). PMID 37660126 ([Link]
118. Guthold M, Liu W, Sparks EA, Jawerth LM, Peng L, Falvo M, et al. (2007-10-02). "A comparison of
the mechanical and structural properties of fibrin fibers with other protein fibers" ([Link]
[Link]/pmc/articles/PMC3010386). Cell Biochemistry and Biophysics. 49 (3): 165–181.
doi:10.1007/s12013-007-9001-4 ([Link] PMC 3010386
([Link] PMID 17952642 ([Link]
[Link]/17952642).
119. Wang K, Meng X, Guo Z (2021). "Elastin Structure, Synthesis, Regulatory Mechanism and
Relationship With Cardiovascular Diseases" ([Link]
233). Frontiers in Cell and Developmental Biology. 9 596702. doi:10.3389/fcell.2021.596702 (http
s://[Link]/10.3389%2Ffcell.2021.596702). PMC 8670233 ([Link]
es/PMC8670233). PMID 34917605 ([Link]
120. Debelle L, Tamburro AM (February 1999). "Elastin: molecular description and function". The
International Journal of Biochemistry & Cell Biology. 31 (2): 261–272. doi:10.1016/S1357-
2725(98)00098-3 ([Link] PMID 10216959
([Link]

[Link] 27/30
8/3/26, 3:32 PM Protein - Wikipedia

121. Khoury LR, Popa I (November 2019). "Chemical unfolding of protein domains induces shape
change in programmed protein hydrogels" ([Link]
1). Nature Communications. 10 (1) 5439. Bibcode:2019NatCo..10.5439K ([Link]
[Link]/abs/2019NatCo..10.5439K). doi:10.1038/s41467-019-13312-0 ([Link]
41467-019-13312-0). PMC 6884551 ([Link]
PMID 31784506 ([Link]
122. Tan R, Shin J, Heo J, Cole BD, Hong J, Jang Y (October 2020). "Tuning the Structural Integrity
and Mechanical Properties of Globular Protein Vesicles by Blending Crosslinkable and
NonCrosslinkable Building Blocks". Biomacromolecules. 21 (10): 4336–4344.
doi:10.1021/[Link].0c01147 ([Link]
PMID 32955862 ([Link]
123. Souza PC, Alessandri R, Barnoud J, Thallmair S, Faustino I, Grünewald F, et al. (April 2021).
"Martini 3: a general purpose force field for coarse-grained molecular dynamics" ([Link]
l/ws/files/190731140/s41592_021_01098_3.pdf) (PDF). Nature Methods. 18 (4): 382–388.
Bibcode:2021NatCB..18..382S ([Link]
doi:10.1038/s41592-021-01098-3 ([Link]
PMC 12554258 ([Link] PMID 33782607 (http
s://[Link]/33782607).
124. "Piotr Szymczak's Homepage" ([Link] [Link].
Retrieved 2024-05-13.
125. Mapplebeck S, Booth J, Shalashilin D (August 2021). "Simulation of protein pulling dynamics on
second time scale with boxed molecular dynamics" ([Link] The
Journal of Chemical Physics. 155 (8) 085101. Bibcode:2021JChPh.155h5101M ([Link]
[Link]/abs/2021JChPh.155h5101M). doi:10.1063/5.0059321 ([Link]
059321). PMID 34470356 ([Link]
126. Carrion-Vazquez M, Marszalek PE, Oberhauser AF, Fernandez JM (September 1999). "Atomic
force microscopy captures length phenotypes in single proteins" ([Link]
c/articles/PMC18026). Proceedings of the National Academy of Sciences of the United States of
America. 96 (20): 11288–11292. Bibcode:1999PNAS...9611288C ([Link]
bs/1999PNAS...9611288C). doi:10.1073/pnas.96.20.11288 ([Link]
0.11288). PMC 18026 ([Link] PMID 10500169 (ht
tps://[Link]/10500169).
127. Weinreb E, McBride JM, Siek M, Rougemont J, Renault R, Peleg Y, et al. (2025-03-28). "Enzymes
as viscoelastic catalytic machines" ([Link] Nature
Physics. 21 (5): 787–798. Bibcode:2025NatPh..21..787W ([Link]
NatPh..21..787W). doi:10.1038/s41567-025-02825-9 ([Link]
25-9). ISSN 1745-2481 ([Link]
128. McKittrick J, Chen PY, Bodde SG, Yang W, Novitskaya EE, Meyers MA (2012-04-03). "The
Structure, Functions, and Mechanical Properties of Keratin" ([Link]
37-012-0302-8). JOM. 64 (4): 449–468. Bibcode:2012JOM....64d.449M ([Link]
edu/abs/2012JOM....64d.449M). doi:10.1007/s11837-012-0302-8 ([Link]
837-012-0302-8).
129. Yang L, van der Werf KO, Fitié CF, Bennink ML, Dijkstra PJ, Feijen J (March 2008). "Mechanical
properties of native and cross-linked type I collagen fibrils" ([Link]
les/PMC2257912). Biophysical Journal. 94 (6): 2204–2211. Bibcode:2008BpJ....94.2204Y (https://
[Link]/abs/2008BpJ....94.2204Y). doi:10.1529/biophysj.107.111013 ([Link]
g/10.1529%2Fbiophysj.107.111013). PMC 2257912 ([Link]
MC2257912). PMID 18032556 ([Link]

[Link] 28/30
8/3/26, 3:32 PM Protein - Wikipedia

130. Lessen HJ, Fleming PJ, Fleming KG, Sodt AJ (August 2018). "Building Blocks of the Outer
Membrane: Calculating a General Elastic Energy Model for β-Barrel Membrane Proteins" (https://
[Link]/pmc/articles/PMC6191857). Journal of Chemical Theory and Computation.
14 (8): 4487–4497. Bibcode:2018JCTC...14.4487L ([Link]
C...14.4487L). doi:10.1021/[Link].8b00377 ([Link]
PMC 6191857 ([Link] PMID 29979594 (https://
[Link]/29979594).

Further reading
Textbooks

Branden C, Tooze J (1999). Introduction to Protein Structure. New York: Garland Pub. ISBN 978-
0-8153-2305-1.
Murray RF, Harper HW, Granner DK, Mayes PA, Rodwell VW (2006). Harper's Illustrated
Biochemistry. New York: Lange Medical Books/McGraw-Hill. ISBN 978-0-07-146197-9.
Van Holde KE, Mathews CK (1996). Biochemistry ([Link]
Menlo Park, California: Benjamin/Cummings Pub. Co., Inc. ISBN 978-0-8053-3931-4.

History

Tanford C, Reynolds JA (2001). Nature's Robots: A History of Proteins. Oxford New York: Oxford
University Press, USA. ISBN 978-0-19-850466-5.

External links

Databases and projects

NCBI Entrez Protein database ([Link]
NCBI Protein Structure database ([Link]
[Link]/sites/entrez?db=Structure)
Human Protein Reference Database ([Link]
[Link]/)
Human Proteinpedia ([Link]
[Link]/)
Folding@Home (Stanford University) ([Link] Archived ([Link]
g/web/20120908075542/[Link] 2012-09-08 at the
Wayback Machine
Protein Databank in Europe ([Link] (see also PDBeQuips ([Link]
130727184433/[Link] short articles and tutorials on interesting PDB
structures)
Research Collaboratory for Structural Bioinformatics ([Link] (see also Molecule of
the Month ([Link]
[Link]) Archived ([Link]
o?p=education_discussion%2Fmolecule_of_the_month%[Link]) 2020-07-24 at the
Wayback Machine, presenting short accounts on selected proteins from the PDB)
Proteopedia – Life in 3D ([Link] rotatable, zoomable 3D model with wiki
annotations for every known protein molecular structure.
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UniProt the Universal Protein Resource ([Link]

[Link]/)

Tutorials and educational websites

"An Introduction to Proteins" ([Link]
tion-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 (https://
[Link]/web/20050219090405/[Link]

Retrieved from "[Link]

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