Figure 1: In the classic cyclol reaction, two peptide groups are linked by a N-C’ bond, converting the carbonyl oxygen into a hydroxyl group. Although this reaction occurs in a few cyclic peptides, it is disfavored by free energy, mainly because it eliminates the resonance stabilization of the peptide bond. This reaction was the basis of Dorothy Wrinch's cyclol model of proteins.

The cyclol hypothesis is the first structural model of a folded, globular protein.^[1] It was developed by Dorothy Wrinch in the late 1930s, and was based on three assumptions. Firstly, the hypothesis assumes that two peptide groups can be crosslinked by a cyclol reaction (Figure 1); these crosslinks are covalent analogs of non-covalent hydrogen bonds between peptide groups. These reactions have been observed in the ergopeptides and other compounds. Secondly, it assumes that, under some conditions, amino acids will naturally make the maximum possible number of cyclol crosslinks, resulting in cyclol molecules (Figure 2) and cyclol fabrics (Figure 3). These cyclol molecules and fabrics have never been observed. Finally, the hypothesis assumes that globular proteins have a tertiary structure corresponding to Platonic solids and semiregular polyhedra formed of cyclol fabrics with no free edges. Such "closed cyclol" molecules have not been observed either. Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... The free energy is a measure of the amount of mechanical (or other) work that can be extracted from a system, and is helpful in engineering applications. ... Resonance in chemistry is a tool used (predominately in organic chemistry) to represent certain types of molecular structures. ... A peptide bond is a chemical bond formed between two molecules when the carboxyl group of one molecule reacts with the amino group of the other molecule, releasing a molecule of water (H2O). ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... In biochemistry, the tertiary structure of a protein is its overall shape. ... Protein folding is the process by which a protein assumes its characteristic functional shape or tertiary structure, also known as the native state. ... Globular proteins, or spheroproteins are one of the two main protein classes, comprising globelike proteins that are more or less soluble in aqueous solutions (where they form colloidal solutions). ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... A peptide bond is a chemical bond formed between two molecules when the carboxyl group of one molecule reacts with the amino group of the other molecule, releasing a molecule of water (H2O). ... An example of a quadruple hydrogen bond between a self-assembled dimer complex reported by Meijer and coworkers. ... Chemical structure of ergoline Ergoline is a chemical compound whose structure serves as the skeleton for a diverse range of alkaloids and synthetic drugs. ... In biochemistry, the tertiary structure of a protein is its overall shape. ... In geometry, a Platonic solid is a convex regular polyhedron. ... A semiregular polyhedron is a geometric shape constructed from a finite number of regular polygon faces with every face edge shared by one other face, and with every vertex containing the same sequence of faces, and, moreover, for every two vertices there is an isometry mapping one into the other. ...

Although later data demonstrated that this original model for the structure of globular proteins needed to be amended, several elements of the cyclol model were verified, such as the cyclol reaction itself and the hypothesis that hydrophobic interactions are chiefly responsible for protein folding. The cyclol hypothesis stimulated many scientists to research questions in protein structure and chemistry, and was a precursor of the more accurate models hypothesized for the DNA double helix and protein secondary structure. The proposal and testing of the cyclol model also provides an excellent illustration of empirical falsifiability acting as part of the scientific method. Proteins are an important class of biological macromolecules present in all biological organisms, made up of such elements as carbon, hydrogen, nitrogen, oxygen and sulfur. ... Hydrophobe (from the Greek (hydros) water and (phobos) fear) in chemistry refers to the physical property of a molecule that is repelled by water. ... Protein folding is the process by which a protein assumes its characteristic functional shape or tertiary structure, also known as the native state. ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ... A representation of the 3D structure of the Myoglobin protein. ... A central concept in science and the scientific method is that all evidence must be empirical, or empirically based, that is, dependent on evidence or consequences that are observable by the senses. ... In science and the philosophy of science, falsifiability is the logical property of empirical statements, related to contingency and defeasibility, that they must admit of logical counterexamples. ... Scientific method is a body of techniques for investigating phenomena and acquiring new knowledge, as well as for correcting and integrating previous knowledge. ...

Historical context

By the mid-1930s, analytical ultracentrifugation studies by Theodor Svedberg had shown that proteins had a well-defined chemical structure, and were not aggregations of small molecules.^[2] The same studies appeared to show that the molecular weight of proteins fell into a few well-defined classes related by integers,^[3] such as M_w = 2^p3^q Da, where p and q are nonnegative integers.^[4] However, it was difficult to determine the exact molecular weight and number of amino acids in a protein. Svedberg had also shown that a change in solution conditions could cause a protein to disassemble into small subunits, now known as a change in quaternary structure.^[5] The ultracentrifuge is a centrifuge optimized for spinning a rotor at very high speeds, capable of generating acceleration as high as 1,000,000 G (9,800 km/s²) There are two kinds of ultracentrifuges, the preparative and the analytical ultracentrifuge. ... Theodor (The) Svedberg (August 30, 1884 – February 25, 1971) was a Swedish chemist and Nobel laureate. ... The unified atomic mass unit (u), or Dalton (Da), is a small unit of mass used to express atomic and molecular masses. ... In biochemistry, many proteins are actually assemblies of more than one protein (polypeptide) molecule, which in the context of the larger assemblage are known as protein subunits. ...

The chemical structure of proteins was still under debate at that time.^[6] The most accepted (and ultimately correct) hypothesis was that proteins are linear polypeptides, i.e., unbranched polymers of amino acids linked by peptide bonds.^[7][8] However, a typical protein is remarkably long — hundreds of amino-acid residues — and several distinguished scientists were unsure whether such long, linear macromolecules could be stable in solution.^[9][10] Further doubts about the polypeptide nature of proteins arose because some enzymes were observed to cleave proteins but not peptides, whereas other enzymes cleave peptides but not folded proteins.^[11] Attempts to synthesize proteins in the test-tube were unsuccessful, mainly due to the chirality of amino acids; naturally occurring proteins are composed of only left-handed amino acids. Hence, alternative chemical models of proteins were considered, such as the diketopiperazine hypothesis of Emil Abderhalden.^[12][13] However, no alternative model had yet explained why proteins yield only amino acids and peptides upon hydrolysis and proteolysis. As clarified by Linderstrøm-Lang,^[14] these proteolysis data showed that denatured proteins were polypeptides, but no data had yet been obtained about the structure of folded proteins; thus, denaturation could involve a chemical change that converted folded proteins into polypeptides. A protein primary structure is a chain of amino acids. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Peptides are the family of molecules formed from the linking, in a defined order, of various amino acids. ... A polymer is a substance composed of molecules with large molecular mass composed of repeating structural units, or monomers, connected by covalent chemical bonds. ... Phenylalanine is one of the standard amino acids. ... A peptide bond is a chemical bond formed between two molecules when the carboxyl group of one molecule reacts with the amino group of the other molecule, releasing a molecule of water (H2O). ... Phenylalanine is one of the standard amino acids. ... A macromolecule is a large molecule with a large molecular mass bonded covalently, but generally the use of the term is restricted to polymers and molecules which structurally include polymers. ... A protein primary structure is a chain of amino acids. ... Neuraminidase ribbon diagram An enzyme (in Greek en = in and zyme = blend) is a protein, or protein complex, that catalyzes a chemical reaction and also controls the 3D orientation of the catalyzed substrates. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... The term chiral (pronounced ) is used to describe an object which is non-superimposable on its mirror image. ... Phenylalanine is one of the standard amino acids. ... Emil Abderhalden (9 March 1877 - 5 August 1950) was a Swiss biochemist and physiologist. ... Kaj Ulrik Linderstrøm-Lang (Nov. ... Irreversible egg protein denaturation and loss of solubility, caused by the high temperature (while cooking it) In biochemistry, denaturation is a structural change in biomolecules such as nucleic acids and proteins, such that they are no longer in their native state, and their shape which allows for optimal activity. ...

The process of protein denaturation (as distinguished from coagulation) had been discovered in 1910 by Harriette Chick and Charles Martin,^[15] but its nature was still mysterious. Tim Anson and Alfred Mirsky had shown that denaturation was a reversible, two-state process^[16] that results in many chemical groups becoming available for chemical reactions, including cleavage by enzymes.^[17] In 1929, Hsien Wu hypothesized correctly that denaturation corresponded to protein unfolding, a purely conformational change that resulted in the exposure of amino-acid side chains to the solvent.^[18] Wu's hypothesis was also advanced independently in 1936 by Mirsky and Linus Pauling.^[19] Nevertheless, protein scientists could not exclude the possibility that denaturation corresponded to a chemical change in the protein structure,^[17] a hypothesis that was considered a (distant) possibility until the 1950s.^[20][21] A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Irreversible egg protein denaturation and loss of solubility, caused by the high temperature (while cooking it) In biochemistry, denaturation is a structural change in biomolecules such as nucleic acids and proteins, such that they are no longer in their native state, and their shape which allows for optimal activity. ... Coagulation is a complex process by which blood forms solid clots. ... Dame Harriette Chick (January 6, 1875 - July 9, 1977) was a notable British nutritionist. ... Charles James Martin (9 January 1866 - 1955) was a British scientist who did seminal work on protein denaturation, nutrition, snake toxins and other medical topics. ... Mortimer (Tim) Louis Anson (1901- 16 October 1968) was an early protein scientist. ... Alfred Ezra Mirsky (October 17, 1900—June 19, 1974) was a pioneer in molecular biology. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... Hsien Wu (24 November 1893 - 8 August 1959) was an early protein scientist who was the first to propose that protein denaturation was a purely conformational change, i. ... Phenylalanine is one of the standard amino acids. ... Linus Carl Pauling (February 28, 1901 – August 19, 1994) was an American quantum chemist and biochemist. ...

X-ray crystallography had just begun as a discipline in 1911, and had advanced relatively rapidly from simple salt crystals to crystals of complex molecules such as cholesterol. However, even the smallest proteins have over 1000 atoms, which makes determining their structure far more complex. In 1934, Dorothy Crowfoot Hodgkin had taken crystallographic data on the structure of the small protein, insulin, although the structure of that and other proteins were not solved until the late 1960s. However, pioneering X-ray fiber diffraction data had been collected in the early 1930s for many natural fibrous proteins such as wool and hair by William Astbury, who proposed rudimentary models of secondary structure elements such as the alpha helix and the beta sheet. X-ray crystallography, also known as single-crystal X-ray diffraction, is the oldest and most common crystallographic method for determining the structure of molecules. ... Cholesterol is a sterol (a combination steroid and alcohol) and a lipid found in the cell membranes of all body tissues, and transported in the blood plasma of all animals. ... Dorothy Mary Crowfoot Hodgkin, OM , FRS (12 May 1910 – 29 July 1994) was a British founder of protein crystallography. ... Insulin (from Latin insula, island, as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormone that regulates carbohydrate metabolism. ... In the NATO phonetic alphabet, X-ray represents the letter X. An X-ray picture (radiograph) taken by Röntgen An X-ray is a form of electromagnetic radiation with a wavelength approximately in the range of 5 pm to 10 nanometers (corresponding to frequencies in the range 30 PHz... Fiber diffraction is a scattering technique in which molecular structure is determined from scattering data (usually of X-rays or electrons) from filaments composed of a regular array of molecules distinguished by a single direction (the fiber axis). ... Fibrous proteins, also called scleroproteins, are long filamentous protein molecules that form one of the two main classes of tertiary structure protein (the other being globular proteins). ... William Astbury (1898-1961) was an English biochemist who made X-ray diffraction studies of nucleic acid in 1937. ... A representation of the 3D structure of the Myoglobin protein. ... Side view of an α-helix of alanine residues in atomic detail. ... Diagram of β-pleated sheet with H-bonding between protein strands The β sheet (also β-pleated sheet) is the second form of regular secondary structure in proteins — the first is the alpha helix — consisting of beta strands connected laterally by three or more hydrogen bonds, forming a generally twisted, pleated sheet. ...

Since protein structure was so poorly understood in the 1930s, the physical interactions responsible for stabilizing that structure were likewise unknown. Astbury hypothesized that the structure of fibrous proteins was stabilized by hydrogen bonds in β-sheets.^[22][23] The idea that globular proteins are also stabilized by hydrogen bonds was proposed by Dorothy Jordan Lloyd^[24][25] in 1932, and championed later by Alfred Mirsky and Linus Pauling.^[19] At a 1933 lecture by Astbury to the Oxford Junior Scientific Society, physicist Frederick Frank suggested that the fibrous protein α-keratin might be stabilized by an alternative mechanism, namely, covalent crosslinking of the peptide bonds by the cyclol reaction above.^[26] The cyclol crosslink draws the two peptide groups close together; the N and C atoms are separated by ~1.5 Å, whereas they are separated by ~3 Å in a typical hydrogen bond. The idea intrigued J. D. Bernal, who suggested it to the mathematician Dorothy Wrinch as possibly useful in understanding protein structure. Proteins are an important class of biological macromolecules present in all biological organisms, made up of such elements as carbon, hydrogen, nitrogen, oxygen and sulfur. ... William Astbury (1898-1961) was an English biochemist who made X-ray diffraction studies of nucleic acid in 1937. ... Fibrous proteins, also called scleroproteins, are long filamentous protein molecules that form one of the two main classes of tertiary structure protein (the other being globular proteins). ... An example of a quadruple hydrogen bond between a self-assembled dimer complex reported by Meijer and coworkers. ... Diagram of β-pleated sheet with H-bonding between protein strands The β sheet (also β-pleated sheet) is the second form of regular secondary structure in proteins — the first is the alpha helix — consisting of beta strands connected laterally by three or more hydrogen bonds, forming a generally twisted, pleated sheet. ... Globular proteins, or spheroproteins are one of the two main protein classes, comprising globelike proteins that are more or less soluble in aqueous solutions (where they form colloidal solutions). ... Dorothy Jordan Lloyd ( 1889 - 21 November 1946 ) was an early protein scientist who studied the interactions of water with proteins, particularly gelatin. ... Alfred Ezra Mirsky (October 17, 1900—June 19, 1974) was a pioneer in molecular biology. ... Linus Carl Pauling (February 28, 1901 – August 19, 1994) was an American quantum chemist and biochemist. ... Frederick Charles Frank (1911-1998) was a physicist associated with the Engineering Laboratory of Oxford University, and later with Bristol University. ... A peptide bond is a chemical bond formed between two molecules when the carboxyl group of one molecule reacts with the amino group of the other molecule, releasing a molecule of water (H2O). ... An angstrom, angström, or Ã¥ngström (symbol Ã…) is a unit of length. ... An angstrom, angström, or Ã¥ngström (symbol Ã…) is a unit of length. ... An example of a quadruple hydrogen bond between a self-assembled dimer complex reported by Meijer and coworkers. ... John Desmond Bernal (1901–1971) was an Irish-born scientist (from Nenagh, County Tipperary), known for pioneering X-ray crystallography. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ...

Basic theory

Figure 2: The alanine cyclol-6 molecule proposed by Dorothy Wrinch is a cyclic hexapeptide in which three peptide groups are fused by cyclol reactions into a central ring. The three outer (unfused) peptide groups are not planar, but have dihedral angle ω=60°. The three red atoms in the central ring represent the hydroxyl groups formed by the cyclol reactions, whereas the three outer red atoms represent the oxygens of carbonyl groups. The inner oxygen atoms are separated by only 2.45 Å, which is extremely close even for hydrogen-bonded atoms. This hypothetical molecule has not been observed in nature.

Wrinch developed this suggestion into a full-fledged model of protein structure. The basic cyclol model was laid out in her first paper (1936).^[27] She noted the possibility that polypeptides might cyclize to form closed rings (true) and that these rings might form internal crosslinks through the cyclol reaction (also true, although rare). Assuming that the cyclol form of the peptide bond could be more stable than the amide form, Wrinch concluded that certain cyclic peptides would naturally make the maximal number of cyclol bonds (such as cyclol 6, Figure 2). Such cyclol molecules would have hexagonal symmetry, if the chemical bonds were taken as having the same length, roughly 1.5 Å; for comparison, the N-C and C-C bonds have the lengths 1.42 Å and 1.54 Å, respectively. Image File history File links Size of this preview: 800 × 589 pixelsFull resolution (926 × 682 pixel, file size: 132 KB, MIME type: image/png) Stick image of the cyclol-6 molecule proposed by Dorothy Maud Wrinch in 1936 (Nature, _137_, 411-412). ... Image File history File links Size of this preview: 800 × 589 pixelsFull resolution (926 × 682 pixel, file size: 132 KB, MIME type: image/png) Stick image of the cyclol-6 molecule proposed by Dorothy Maud Wrinch in 1936 (Nature, _137_, 411-412). ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... A peptide bond is a chemical bond formed between two molecules when the carboxyl group of one molecule reacts with the amino group of the other molecule, releasing a molecule of water (H2O). ... An angstrom, angström, or Ã¥ngström (symbol Ã…) is a unit of length. ... An example of a quadruple hydrogen bond between a self-assembled dimer complex reported by Meijer and coworkers. ... Properties In chemistry and physics, an atom (Greek ἄτομος or átomos meaning indivisible) is the smallest particle still characterizing a chemical element. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Proteins are an important class of biological macromolecules present in all biological organisms, made up of such elements as carbon, hydrogen, nitrogen, oxygen and sulfur. ... Peptides are the family of molecules formed from the linking, in a defined order, of various amino acids. ... alpha amanitin bacitracin cyclosporine Cyclic peptides (or cyclic proteins) are polypeptide chains whose amino and carboxyl termini are themselves linked together with a peptide bond, forming a circular chain. ... A peptide bond is a chemical bond formed between two molecules when the carboxyl group of one molecule reacts with the amino group of the other molecule, releasing a molecule of water (H2O). ... Peptides (from the Greek πεπτος, digestible), are the family of short molecules formed from the linking, in a defined order, of various α-amino acids. ... A chemical bond is the physical process responsible for the attractive interactions between atoms and molecules, and that which confers stability to diatomic and polyatomic chemical compounds. ... An angstrom, angström, or Ã¥ngström (symbol Ã…) is a unit of length. ... An angstrom, angström, or Ã¥ngström (symbol Ã…) is a unit of length. ... An angstrom, angström, or Ã¥ngström (symbol Ã…) is a unit of length. ...

These rings can be extended indefinitely to form a cyclol fabric (Figure 3). Such fabrics exhibit a long-range, quasi-crystalline order that Wrinch felt was likely in proteins, since they must pack hundreds of residues densely. Another interesting feature of such molecules and fabrics is that their amino-acid side chains point axially upwards from only face; the opposite face has no side chains. Thus, one face is completely independent of the primary sequence of the peptide, which Wrinch conjectured might account for sequence-independent properties of proteins. Phenylalanine is one of the standard amino acids. ... A protein primary structure is a chain of amino acids. ... Peptides (from the Greek πεπτος, digestible), are the family of short molecules formed from the linking, in a defined order, of various α-amino acids. ...

In her initial article, Wrinch stated clearly that the cyclol model was merely a working hypothesis, a potentially valid model of proteins that would have to be checked. Her goals in this article and its successors were to propose a well-defined testable model, to work out the consequences of its assumptions and to make predictions that could be tested experimentally. In these goals, she succeeded; however, within a few years, experiments and further modeling showed that the cyclol hypothesis was untenable as a model for globular proteins.

Stabilizing energies

Figure 3: Stick model of the alanine cyclol fabric proposed by Dorothy Wrinch. The cyclol fabric is conceptually similar to a beta sheet, but more uniform and laterally denser. The fabric has large "lacunae" arranged in a hexagonal pattern, in which three C^β atoms (shown in green) and three H^α atoms (shown in white) converge on a (relatively) empty spot in the fabric. The two sides of the fabric are not equivalent; all the C^β atoms emerge from the same side, which is the "upper" side here. The red atoms represent hydroxyl groups (not carbonyl groups) and emerge (in sets of three) from both sides of the fabric; the blue atoms represent nitrogen. This hypothetical structure has not been observed in nature.

In two tandem Letters to the Editor (1936),^[28][29] Wrinch and Frank addressed the question of whether the cyclol form of the peptide group was indeed more stable than the amide form. A relatively simple calculation showed that the cyclol form is significantly less stable than the amide form. Therefore, the cyclol model would have to be abandoned unless a compensating source of energy could be identified. Initially, Frank proposed that the cyclol form might be stabilized by better interactions with the surrounding solvent; later, Wrinch and Irving Langmuir hypothesized that hydrophobic association of nonpolar sidechains provides stabilizing energy to overcome the energetic cost of the cyclol reactions.^[30][31] Image File history File links Size of this preview: 700 × 600 pixelsFull resolution (798 × 684 pixel, file size: 345 KB, MIME type: image/png) Stick image of the cyclol fabric proposed by Dorothy Maud Wrinch in 1936 (Nature, _137_, 411-412). ... Image File history File links Size of this preview: 700 × 600 pixelsFull resolution (798 × 684 pixel, file size: 345 KB, MIME type: image/png) Stick image of the cyclol fabric proposed by Dorothy Maud Wrinch in 1936 (Nature, _137_, 411-412). ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Diagram of β-pleated sheet with H-bonding between protein strands The β sheet (also β-pleated sheet) is the second form of regular secondary structure in proteins — the first is the alpha helix — consisting of beta strands connected laterally by three or more hydrogen bonds, forming a generally twisted, pleated sheet. ... Irving Langmuir at home (c. ...

The lability of the cyclol bond was seen as an advantage of the model, since it provided a natural explanation for the properties of denaturation; reversion of cyclol bonds to their more stable amide form would open up the structure and allows those bonds to be attacked by proteases, consistent with experiment.^[32][33] Early studies showed that proteins denatured by pressure are often in a different state than the same proteins denatured by high temperature, which was interpreted as possibly supporting the cyclol model of denaturation.^[34] Irreversible egg protein denaturation and loss of solubility, caused by the high temperature (while cooking it) In biochemistry, denaturation is a structural change in biomolecules such as nucleic acids and proteins, such that they are no longer in their native state, and their shape which allows for optimal activity. ... Proteases (proteinases, peptidases, or proteolytic enzymes) are enzymes that break peptide bonds between amino acids of proteins. ... Irreversible egg protein denaturation and loss of solubility, caused by the high temperature (while cooking it) In biochemistry, denaturation is a structural change in biomolecules such as nucleic acids and proteins, such that they are no longer in their native state, and their shape which allows for optimal activity. ... The use of water pressure - the Captain Cook Memorial Jet in Lake Burley Griffin in Canberra, Australia. ... This article includes a list of works cited or a list of external links, but its sources remain unclear because it lacks in-text citations. ...

The Langmuir-Wrinch hypothesis of hydrophobic stabilization shared in the downfall of the cyclol model, owing mainly to the influence of Linus Pauling, who favored the hypothesis that protein structure was stabilized by hydrogen bonds. Another twenty years had to pass before hydrophobic interactions were recognized as the chief driving force in protein folding.^[35] Linus Carl Pauling (February 28, 1901 – August 19, 1994) was an American quantum chemist and biochemist. ... An example of a quadruple hydrogen bond between a self-assembled dimer complex reported by Meijer and coworkers. ...

Steric complementarity

In her third paper on cyclols (1936),^[36] Wrinch noted that many "physiologically active" substances such as steroids are composed of fused hexagonal rings of carbon atoms and, thus, might be sterically complementary to the face of cyclol molecules without the amino-acid side chains. Wrinch proposed that steric complementarity was one of chief factors in determining whether a small molecule would bind to a protein. Steroid skeleton of lanosterol. ... Phenylalanine is one of the standard amino acids. ...

Wrinch speculated that proteins are responsible for the synthesis of all biological molecules. Noting that cells digest their proteins only under extreme starvation conditions, Wrinch further speculated that life could not exist without proteins.

Hybrid models

From the beginning, the cyclol reaction was considered as a covalent analog of the hydrogen bond. Therefore, it was natural to consider hybrid models with both types of bonds. This was the subject of Wrinch's fourth paper on the cyclol model (1936),^[37] written together with Dorothy Jordan Lloyd, who first proposed that globular proteins are stabilized by hydrogen bonds.^[24] A follow-up paper was written in 1937 that referenced other researchers on hydrogen bonding in proteins, such as Maurice Loyal Huggins and Linus Pauling.^[38] An example of a quadruple hydrogen bond between a self-assembled dimer complex reported by Meijer and coworkers. ... Dorothy Jordan Lloyd ( 1889 - 21 November 1946 ) was an early protein scientist who studied the interactions of water with proteins, particularly gelatin. ... Maurice Loyal Huggins (19 September 1897- 17 December 1981) was a scientist who independently conceived the idea of hydrogen bonding and who was an early advocate for their role in stabilizing protein secondary structure. ... Linus Carl Pauling (February 28, 1901 – August 19, 1994) was an American quantum chemist and biochemist. ...

Wrinch also wrote a paper with William Astbury, noting the possibility of a keto-enol isomerization of the >C^αH^α and an amide carbonyl group >C=O, producing a crosslink >C^α-C(OH^α)< and again converting the oxygen to a hydroxyl group.^[39] Such reactions could yield five-membered rings, whereas the classic cyclol hypothesis produces six-membered rings. This keto-enol crosslink hypothesis was not developed much further.^[40] William Astbury (1898-1961) was an English biochemist who made X-ray diffraction studies of nucleic acid in 1937. ...

Space-enclosing fabrics

Figure 4: Stick model of the cyclol C₁ protein structure proposed by Dorothy Wrinch. The molecule is a truncated tetrahedron composed of four planar cyclol fabrics, each surrounding one lacuna (48 residues), and joined together pairwise by four residues along each edge (two residues at each corner). Thus, this molecule has 72 amino-acid residues altogether. It is viewed here "face-on", i.e., looking into the lacuna of one cyclol fabric. The side chains (taken here as alanine) all point into the interior of this "cage-like" structure. This hypothetical structure has not been observed in nature.

In her fifth paper on cyclols (1937),^[41] Wrinch identified the conditions under which two planar cyclol fabrics could be joined to make an angle between their planes while respecting the chemical bond angles. She identified a mathematical simplification, in which the non-planar six-membered rings of atoms can be represented by planar "median hexagon"s made from the midpoints of the chemical bonds. This "median hexagon" representation made it easy to see that the cyclol fabric planes can be joined correctly if the dihedral angle between the planes equals the tetrahedral bond angle δ = arccos(-1/3) ≈ 109.47°. Image File history File links Size of this preview: 639 × 600 pixelsFull resolution (748 × 702 pixel, file size: 332 KB, MIME type: image/png) Stick image of the cyclol C1 model of a globular protein, as proposed by Dorothy Maud Wrinch in 1937 (Nature, _139_, 972-973). ... Image File history File links Size of this preview: 639 × 600 pixelsFull resolution (748 × 702 pixel, file size: 332 KB, MIME type: image/png) Stick image of the cyclol C1 model of a globular protein, as proposed by Dorothy Maud Wrinch in 1937 (Nature, _139_, 972-973). ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Phenylalanine is one of the standard amino acids. ... In Aerospace engineering, the dihedral is the angle that the two wings make with each other. ...

A large variety of closed polyhedra meeting this criterion can be constructed, of which the simplest are the truncated tetrahedron, the truncated octahedron, and the octahedron, which are Platonic solids or semiregular polyhedra. Considering the first series of "closed cyclols" (those modeled on the truncated tetrahedron), Wrinch showed that their number of amino acids increased quadratically as 72n², where n is the index of the closed cyclol C_n. Thus, the C₁ cyclol has 72 residues, the C₂ cyclol has 288 residues, etc. Preliminary experimental support for this prediction came from Bergmann and Niemann,^[4] whose amino-acid analyses suggested that proteins were comprised of integer multiples of 288 amino-acid residues (n=2). More generally, the cyclol model of globular proteins accounted for the early analytical ultracentrifugation results of Theodor Svedberg, which suggested that the molecular weights of proteins fell into a few classes related by integers.^[2][3] The truncated tetrahedron is an Archimedean solid. ... The truncated octahedron, also known as a Mecon, is an Archimedean solid. ... An octahedron (plural: octahedra) is a polyhedron with eight faces. ... In geometry, a Platonic solid is a convex regular polyhedron. ... A semiregular polyhedron is a geometric shape constructed from a finite number of regular polygon faces with every face edge shared by one other face, and with every vertex containing the same sequence of faces, and, moreover, for every two vertices there is an isometry mapping one into the other. ... In mathematics, a function or sequence is said to exhibit quadratic growth when its values are proportional to the square of the function argument or sequence position, in the limit as the argument or sequence position goes to infinity. ... Phenylalanine is one of the standard amino acids. ... The ultracentrifuge is a centrifuge optimized for spinning a rotor at very high speeds, capable of generating acceleration as high as 1,000,000 G (9,800 km/s²) There are two kinds of ultracentrifuges, the preparative and the analytical ultracentrifuge. ... Theodor (The) Svedberg (August 30, 1884 – February 25, 1971) was a Swedish chemist and Nobel laureate. ... The molecular mass of a substance (less accurately called molecular weight and abbreviated as MW) is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ...

The cyclol model was consistent with the general properties then attributed to folded proteins.^[42] (1) Centrifugation studies had shown that folded proteins were significantly denser than water (~1.4 g/mL) and, thus, tightly packed; Wrinch assumed that dense packing should imply regular packing. (2) Despite their large size, some proteins crystallize readily into symmetric crystals, consistent with the idea of symmetric faces that match up upon association. (3) Proteins bind metal ions; since metal-binding sites must have specific bond geometries (e.g., octahedral), it was plausible to assume that the entire protein also had similarly crystalline geometry. (4) As described above, the cyclol model provided a simple chemical explanation of denaturation and the difficulty of cleaving folded proteins with proteases. (5) Proteins were assumed to be responsible for the synthesis of all biological molecules, including other proteins. Wrinch noted that a fixed, uniform structure would be useful for proteins in templating their own synthesis, analogous to the Watson-Francis Crick concept of DNA templating its own replication. Given that many biological molecules such as sugars and sterols have a hexagonal structure, it was plausible to assume that their synthesizing proteins likewise had a hexagonal structure. Wrinch summarized her model and the supporting molecular-weight experimental data in three review articles.^[43] BIC pen cap, about 1 gram. ... The liter (spelled liter in American English and litre in Commonwealth English) is a unit of volume. ... Irreversible egg protein denaturation and loss of solubility, caused by the high temperature (while cooking it) In biochemistry, denaturation is a structural change in biomolecules such as nucleic acids and proteins, such that they are no longer in their native state, and their shape which allows for optimal activity. ... James Dewey Watson born April 6, 1928) is an American molecular biologist, best known as one of the co-discoverers of the structure of the DNA molecule. ... Francis Harry Compton Crick OM FRS (8 June 1916 – 28 July 2004) was an English molecular biologist, physicist, and neuroscientist, who is most noted for being one of the co-discoverers of the structure of the DNA molecule in 1953. ... Lactose is a disaccharide found in milk. ... Sterols, or steroid alcohols are a subgroup of steroids with a hydroxyl group in the 3-position of the A-ring. ...

Predicted protein structures

Having proposed a model of globular proteins, Wrinch investigated whether it was consistent with the available structural data. She hypothesized that bovine tuberculin protein (523) was a C₁ closed cyclol consisting of 72 residues^[44] and that the digestive enzyme pepsin was a C₂ closed cyclol of 288 residues.^[45][46] These residue-number predictions were difficult to verify, since the methods then available to measure the mass of proteins were inaccurate, such as analytical ultracentrifugation and chemical methods. Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... Pepsin is a digestive protease (EC 3. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... The ultracentrifuge is a centrifuge optimized for spinning a rotor at very high speeds, capable of generating acceleration as high as 1,000,000 G (9,800 km/s²) There are two kinds of ultracentrifuges, the preparative and the analytical ultracentrifuge. ...

Wrinch also predicted that insulin was a C₂ closed cyclol consisting of 288 residues. Limited X-ray crystallographic data were available for insulin which Wrinch interpreted as "confirming" her model.^[47] However, this interpretation drew rather severe criticism for being premature.^[48] Careful studies of the Patterson diagrams of insulin taken by Dorothy Crowfoot Hodgkin showed that they were roughly consistent with the cyclol model; however, the agreement was not good enough to claim that the cyclol model was confirmed.^[49] Insulin (from Latin insula, island, as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormone that regulates carbohydrate metabolism. ... Insulin (from Latin insula, island, as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormone that regulates carbohydrate metabolism. ... Dorothy Mary Crowfoot Hodgkin, OM , FRS (12 May 1910 – 29 July 1994) was a British founder of protein crystallography. ...

Downfall

Figure 5: Spacefilling diagram of the alanine cyclol fabric, as seen from the side where none of the C^β atoms emerge. This Figure shows the three-fold symmetry of the fabric and also its extraordinary density; for example, in the "lacunae" — where three C^β atoms (shown in green) and three H^α atoms (shown as white triangles) converge — the carbons and hydrogens are separated by only 1.68 Å. The larger green spheres represent the C^β atoms; the C^α atoms are generally not visible, except as little triangles next to the blue nitrogen atoms. As before, the red atoms represent hydroxyl groups, not carbonyl oxygen atoms.

The cyclol fabric was shown to be implausible for several reasons. Hans Neurath and Henry Bull showed that the dense packing of side chains in the cyclol fabric was inconsistent with the experimental density observed in protein films.^[50] Maurice Huggins calculated that several non-bonded atoms of the cyclol fabric would approach more closely than allowed by their van der Waals radii; for example, the inner H^α and C^α atoms of the lacunae would be separated by only 1.68 Å (Figure 5).^[51] Haurowitz showed chemically that the outside of proteins could not have a large number of hydroxyl groups, a key prediction of the cyclol model,^[52] whereas Meyer and Hohenemser showed that cyclol condensations of amino acids did not exist even in minute quantities as a transition state.^[53] More general chemical arguments against the cyclol model were given by Bergmann and Niemann^[54] and by Neuberger.^[55][56] Infrared spectroscopic data showed that the number of carbonyl groups in a protein did not change upon hydrolysis,^[57] and that intact, folded proteins have a full complement of amide carbonyl groups;^[58] both observations contradict the cyclol hypothesis that such carbonyls are converted to hydroxyl groups in folded proteins. Finally, proteins were known to contain proline in significant quantities (typically 5%); since proline lacks the amide hydrogen and its nitrogen already forms three covalent bonds, proline seems incapable of the cyclol reaction and of being incorporated into a cyclol fabric. An encyclopedic summary of the chemical and structural evidence against the cyclol model was given by Pauling and Niemann.^[59] Moreover, a supporting piece of evidence — the result that all proteins contain an integer multiple of 288 amino-acid residues^[4] — was likewise shown to be incorrect in 1939.^[60] Image File history File links Size of this preview: 790 × 600 pixelsFull resolution (942 × 715 pixel, file size: 1. ... Image File history File links Size of this preview: 790 × 600 pixelsFull resolution (942 × 715 pixel, file size: 1. ... An angstrom, angström, or Ã¥ngström (symbol Ã…) is a unit of length. ... Hans Neurath (1909- 12 April 2002) was an early protein scientist. ... Maurice Loyal Huggins (19 September 1897- 17 December 1981) was a scientist who independently conceived the idea of hydrogen bonding and who was an early advocate for their role in stabilizing protein secondary structure. ... The van der Waals radius of an atom is the radius of an imaginary hard sphere which can be used to model the atom for many purposes. ... An angstrom, angström, or Ã¥ngström (symbol Ã…) is a unit of length. ... Proline is an α-amino acid with the chemical formula HO2CCH(NH[CH2)3]. L-Proline is one of the twenty DNA-encoded amino acids. ... Phenylalanine is one of the standard amino acids. ...

Wrinch replied to the steric-clash, free-energy, chemical and residue-number criticisms of the cyclol model. On steric clashes, she noted that small deformations of the bond angles and bond lengths would allow these steric clashes to be relieved, or at least reduced to a reasonable level.^[61] She noted that distances between non-bonded groups within a single molecule can be shorter than expected from their van der Waals radii, e.g., the 2.93 Å distance between methyl groups in hexamethylbenzene. Regarding the free-energy penalty for the cyclol reaction, Wrinch disagreed with Pauling's calculations and stated that too little was known of intramolecular energies to rule out the cyclol model on that basis alone.^[61] In reply to the chemical criticisms, Wrinch suggested that the model compounds and simple bimolecular reactions studied need not pertain to the cyclol model, and that steric hindrance may have prevented the surface hydroxyl groups from reacting.^[62] On the residue-number criticism, Wrinch extended her model to allow for other numbers of residues. In particular, she produced a "minimal" closed cyclol of only 48 residues,^[63] and, on that (incorrect) basis, may have been the first to suggest that the insulin monomer had a molecular weight of roughly 6000 Da.^[64][65] The van der Waals radius of an atom is the radius of an imaginary hard sphere which can be used to model the atom for many purposes. ... An angstrom, angström, or Ã¥ngström (symbol Ã…) is a unit of length. ... Insulin (from Latin insula, island, as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormone that regulates carbohydrate metabolism. ... The unified atomic mass unit (u), or Dalton (Da), is a small unit of mass used to express atomic and molecular masses. ...

Therefore, she maintained that the cyclol model of globular proteins was still potentially viable^[66][67] and even proposed the cyclol fabric as a component of the cytoskeleton.^[68] However, most protein scientists ceased to believe in it and Wrinch turned her scientific attention to mathematical problems in X-ray crystallography, to which she contributed significantly. One exception was physicist Gladys Anslow, Wrinch's colleague at Smith College, who studied the ultraviolet absorption spectra of proteins and peptides in the 1940s and allowed for the possibility of cyclols in interpreting her results.^[69][70] As the sequence of insulin began to be determined by Frederick Sanger, Anslow published a three-dimensional cyclol model with sidechains,^[71] based on the backbone of Wrinch's 1948 "minimal cyclol" model.^[63] The eukaryotic cytoskeleton. ... X-ray crystallography, also known as single-crystal X-ray diffraction, is the oldest and most common crystallographic method for determining the structure of molecules. ... Smith College, located in Northampton, Massachusetts, is the largest womens college in the United States []. Smith admits only female undergraduates, but admits both men and women as graduate students. ... “UV” redirects here. ... Look up absorption in Wiktionary, the free dictionary. ... A protein primary structure is a chain of amino acids. ... Insulin (from Latin insula, island, as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormone that regulates carbohydrate metabolism. ... Frederick Sanger, OM, CH, CBE, FRS (born 13 August 1918) is an English biochemist and a two time Nobel laureate in Chemistry. ...

Partial redemption

Figure 6: A typical azacyclol molecule (red) in a rapid equilibrium with its bislactam macrocycle form (blue). The amide groups of the bislactam form are crosslinked in the cyclol form; these two tautomers have similar stability, giving an equilibrium constant of ~1. However, the open form (black) is unstable, and not observed.^[72]

The downfall of the overall cyclol model generally led to a rejection of its elements; one notable exception was J. D. Bernal's short-lived acceptance of the Langmuir-Wrinch hypothesis that protein folding is driven by hydrophobic association.^[73] Nevertheless, cyclol bonds were identified in small, naturally occurring cyclic peptides in the 1950s. Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... A lactam (the noun is a portmanteau of the wods lactone + amide) is a cyclic amide. ... Amide functional group Amides possess a conjugated system spread over the O, C and N atoms, consisting of molecular orbitals occupied by delocalized electrons. ... Tautomers are organic compounds that are interconvertible by a chemical reaction called tautomerization. ... In chemistry, the equilibrium constant is a quantity characterizing a chemical equilibrium in a chemical reaction. ... John Desmond Bernal (1901–1971) was an Irish-born scientist (from Nenagh, County Tipperary), known for pioneering X-ray crystallography. ... Protein folding is the process by which a protein assumes its characteristic functional shape or tertiary structure, also known as the native state. ... alpha amanitin bacitracin cyclosporine Cyclic peptides (or cyclic proteins) are polypeptide chains whose amino and carboxyl termini are themselves linked together with a peptide bond, forming a circular chain. ...

Clarification of the modern terminology is appropriate. The classic cyclol reaction is the addition of the NH amine of a peptide group to the C=O carbonyl group of another; the resulting compound is now called an azacyclol. By analogy, an oxacyclol is formed when an OH hydroxyl group is added to a peptidyl carbonyl group. Likewise, a thiacyclol is formed by adding an SH thiol moiety to a peptidyl carbonyl group.^[74] A peptide bond is a chemical bond formed between two molecules when the carboxyl group of one molecule reacts with the amino group of the other molecule, releasing a molecule of water (H2O). ...

The oxacyclol alkaloid ergotamine from the fungus Claviceps purpurea was the first identified cyclol.^[75] The cyclic depsipeptide serratamolide is also formed by an oxacyclol reaction.^[76] Chemically analogous cyclic thiacyclols have also been obtained.^[77] Classic azacyclols have been observed in small molecules^[78] and tripeptides.^[79] Peptides are naturally produced from the reversion of azacylols,^[80] a key prediction of the cyclol model. Hundreds of cyclol molecules have now been identified, despite Linus Pauling's calculation that such molecules should not exist because of their unfavorably high energy.^[59] Chemical structure of ephedrine, a phenethylamine alkaloid An alkaloid is, strictly speaking, a naturally occurring amine produced by a plant,[1] but amines produced by animals and fungi are also called alkaloids. ... Ergotamine is a vasoconstrictor used for migraine prevention and is sometimes mixed with caffeine. ... For the fictional character, see Fungus the Bogeyman. ... Linus Carl Pauling (February 28, 1901 – August 19, 1994) was an American quantum chemist and biochemist. ...

After a long hiatus during which she worked mainly on the mathematics of X-ray crystallography, Wrinch responded to these discoveries with renewed enthusiasm for the cyclol model and its relevance in biochemistry.^[81] She also published two books describing the cyclol theory and small peptides in general.^[82][83] X-ray crystallography, also known as single-crystal X-ray diffraction, is the oldest and most common crystallographic method for determining the structure of molecules. ...

Illustration of the scientific method

The cyclol model of protein structure is an example of empirical falsifiability acting as part of the scientific method. An original hypothesis is made that accounts for unexplained experimental observations; the consequences of this hypothesis are worked out, leading to predictions that are tested by experiment. In this case, the key hypothesis was that the cyclol form of the peptide group could be favored over the amide form. This hypothesis led to the predictions of the cyclol-6 molecule and the cyclol fabric, which in turn suggested the model of semi-regular polyhedra for globular proteins. A key testable prediction was that a folded protein's carbonyl groups should be largely converted to hydroxyl groups; however, spectroscopic and chemical experiments showed that this prediction was incorrect. The cyclol model also predicts a high lateral density of amino acids in folded proteins and in films that does not agree with experiment. Hence, the cyclol model could be rejected and the search begun for new hypotheses of protein structure, such as the models of the alpha helix proposed in the 1940s and 1950s. A central concept in science and the scientific method is that all evidence must be empirical, or empirically based, that is, dependent on evidence or consequences that are observable by the senses. ... In science and the philosophy of science, falsifiability is the logical property of empirical statements, related to contingency and defeasibility, that they must admit of logical counterexamples. ... Scientific method is a body of techniques for investigating phenomena and acquiring new knowledge, as well as for correcting and integrating previous knowledge. ... Look up Hypothesis in Wiktionary, the free dictionary. ... Proteins are an important class of biological macromolecules present in all biological organisms, made up of such elements as carbon, hydrogen, nitrogen, oxygen and sulfur. ... Side view of an α-helix of alanine residues in atomic detail. ...

It is sometimes argued that the cyclol hypothesis should never have been advanced,^[84][85] because of its a priori flaws, e.g., its steric clashes, its inability to accommodate proline, and the high free energy disfavoring the cyclol reaction itself. Although such flaws rendered the cyclol hypothesis implausible, they did not make it impossible. The cyclol model was the first well-defined structure proposed for globular proteins, and too little was then known of intramolecular forces and protein structure to reject it immediately. It neatly explained several general properties of proteins and accounted for then-anomalous experimental observations. Although generally incorrect, some elements of the cyclol theory were eventually verified, such as the cyclol reactions and the role of hydrophobic interactions in protein folding. A useful comparison is the Bohr model of the hydrogen atom, which was considered implausible from its inception, even by its creator,^[86] yet led the way to the ultimately correct theory of quantum mechanics. Similarly, Linus Pauling proposed a well-defined model of DNA^[87] that was likewise implausible yet thought-provoking to other investigators.^[88][89] The cyclol story is an example of where an area of science progressed by formulating a well-defined hypothesis, testing it and eliminating it as incorrect. Proline is an α-amino acid with the chemical formula HO2CCH(NH[CH2)3]. L-Proline is one of the twenty DNA-encoded amino acids. ... The free energy is a measure of the amount of mechanical (or other) work that can be extracted from a system, and is helpful in engineering applications. ... Hydrophobe (from the Greek (hydros) water and (phobos) fear) in chemistry refers to the physical property of a molecule that is repelled by water. ... Protein folding is the process by which a protein assumes its characteristic functional shape or tertiary structure, also known as the native state. ... The Bohr model of the hydrogen atom, where negatively charged electrons confined to atomic shells encircle a small positively charged atomic nucleus, and that an electron jump between orbits must be accompanied by an emitted or absorbed amount of electromagnetic energy hν. The orbits that the electrons travel in are... General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ... Properties In chemistry and physics, an atom (Greek ἄτομος or átomos meaning indivisible) is the smallest particle still characterizing a chemical element. ... Fig. ... Linus Carl Pauling (February 28, 1901 – August 19, 1994) was an American quantum chemist and biochemist. ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ...

Conversely, the cyclol model is an example of an incorrect scientific theory of great symmetry and beauty, two qualities that can be regarded as signs of "obviously true" scientific theories. For example, the Watson-Crick double helix model of DNA^[89] is sometimes said to be "obvious" because of its plausible hydrogen bonding and symmetry; nevertheless, other, less symmetrical structures of DNA are favored under different conditions.^[90] Similarly, the beautiful theory of general relativity was considered by Albert Einstein as not needing experimental verification; yet even this theory will require revision for consistency with quantum field theory.^[91] The example of the cyclol model illustrates that all scientific theories, even the most beautiful and symmetrical, must be tested by experiment and that no theory is obviously true a priori, only more plausible. Sphere symmetry group o. ... This article does not cite any references or sources. ... James Dewey Watson born April 6, 1928) is an American molecular biologist, best known as one of the co-discoverers of the structure of the DNA molecule. ... Francis Harry Compton Crick OM FRS (8 June 1916 – 28 July 2004) was an English molecular biologist, physicist, and neuroscientist, who is most noted for being one of the co-discoverers of the structure of the DNA molecule in 1953. ... The Double-Helix are an alien race in the Wing Commander science fiction series. ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ... An example of a quadruple hydrogen bond between a self-assembled dimer complex reported by Meijer and coworkers. ... An illustration of a rotating black hole at the center of a galaxy General relativity (GR) (aka general theory of relativity (GTR)) is the geometrical theory of gravitation published by Albert Einstein in 1915/16. ... “Einstein” redirects here. ... Quantum field theory (QFT) is the quantum theory of fields. ...

See also

• Primary structure
• Peptide bond
• Insulin
• Denaturation (biochemistry)
• Dorothy Maud Wrinch
• Linus Pauling

A protein primary structure is a chain of amino acids. ... A peptide bond is a chemical bond formed between two molecules when the carboxyl group of one molecule reacts with the amino group of the other molecule, releasing a molecule of water (H2O). ... Insulin (from Latin insula, island, as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormone that regulates carbohydrate metabolism. ... Irreversible egg protein denaturation and loss of solubility, caused by the high temperature (while cooking it) In biochemistry, denaturation is a structural change in biomolecules such as nucleic acids and proteins, such that they are no longer in their native state, and their shape which allows for optimal activity. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Linus Carl Pauling (February 28, 1901 – August 19, 1994) was an American quantum chemist and biochemist. ...

References

Arne Wilhelm Kaurin Tiselius (Stockholm 10 August 1902 &#8211; Uppsala 29 October 1971), Swedish biochemist. ... Theodor (The) Svedberg (August 30, 1884 – February 25, 1971) was a Swedish chemist and Nobel laureate. ... Theodor (The) Svedberg (August 30, 1884 – February 25, 1971) was a Swedish chemist and Nobel laureate. ... Theodor (The) Svedberg (August 30, 1884 – February 25, 1971) was a Swedish chemist and Nobel laureate. ... Franz Hofmeister (1850-1922) was an early protein scientist, and is famous for his studies of salts that influence the solubility and conformational stability of proteins. ... Hermann Emil Fischer (October 9, 1852 - July 15, 1919) was a German chemist and recipient of the Nobel Prize for Chemistry in 1902. ... Hermann Emil Fischer (October 9, 1852 - July 15, 1919) was a German chemist and recipient of the Nobel Prize for Chemistry in 1902. ... Søren Peder Lauritz Sørensen, born in Havrebjerg, Denmark on January 9, 1868 and died on February 12, 1939, was a Danish chemist. ... Emil Abderhalden (9 March 1877 - 5 August 1950) was a Swiss biochemist and physiologist. ... Emil Abderhalden (9 March 1877 - 5 August 1950) was a Swiss biochemist and physiologist. ... Kaj Ulrik Linderstrøm-Lang (Nov. ... Dame Harriette Chick (January 6, 1875 - July 9, 1977) was a notable British nutritionist. ... Charles James Martin (9 January 1866 - 1955) was a British scientist who did seminal work on protein denaturation, nutrition, snake toxins and other medical topics. ... Dame Harriette Chick (January 6, 1875 - July 9, 1977) was a notable British nutritionist. ... Charles James Martin (9 January 1866 - 1955) was a British scientist who did seminal work on protein denaturation, nutrition, snake toxins and other medical topics. ... Dame Harriette Chick (January 6, 1875 - July 9, 1977) was a notable British nutritionist. ... Charles James Martin (9 January 1866 - 1955) was a British scientist who did seminal work on protein denaturation, nutrition, snake toxins and other medical topics. ... Dame Harriette Chick (January 6, 1875 - July 9, 1977) was a notable British nutritionist. ... Charles James Martin (9 January 1866 - 1955) was a British scientist who did seminal work on protein denaturation, nutrition, snake toxins and other medical topics. ... Mortimer (Tim) Louis Anson (1901- 16 October 1968) was an early protein scientist. ... Alfred Ezra Mirsky (October 17, 1900—June 19, 1974) was a pioneer in molecular biology. ... Mortimer (Tim) Louis Anson (1901- 16 October 1968) was an early protein scientist. ... Alfred Ezra Mirsky (October 17, 1900—June 19, 1974) was a pioneer in molecular biology. ... Linus Carl Pauling (February 28, 1901 – August 19, 1994) was an American quantum chemist and biochemist. ... Hans Neurath (1909- 12 April 2002) was an early protein scientist. ... William Astbury (1898-1961) was an English biochemist who made X-ray diffraction studies of nucleic acid in 1937. ... William Astbury (1898-1961) was an English biochemist who made X-ray diffraction studies of nucleic acid in 1937. ... Dorothy Jordan Lloyd ( 1889 - 21 November 1946 ) was an early protein scientist who studied the interactions of water with proteins, particularly gelatin. ... Dorothy Jordan Lloyd ( 1889 - 21 November 1946 ) was an early protein scientist who studied the interactions of water with proteins, particularly gelatin. ... William Astbury (1898-1961) was an English biochemist who made X-ray diffraction studies of nucleic acid in 1937. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Frederick Charles Frank (1911-1998) was a physicist associated with the Engineering Laboratory of Oxford University, and later with Bristol University. ... Irving Langmuir at home (c. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Irving Langmuir at home (c. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Jordan Lloyd ( 1889 - 21 November 1946 ) was an early protein scientist who studied the interactions of water with proteins, particularly gelatin. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... William Astbury (1898-1961) was an English biochemist who made X-ray diffraction studies of nucleic acid in 1937. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Irving Langmuir at home (c. ... Irving Langmuir at home (c. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Sir William Lawrence Bragg CH, FRS, (31 March 1890 – 1 July 1971) was an Australian physicist who shared the Nobel Prize in Physics in 1915 with his father Sir William Henry Bragg. ... John Desmond Bernal (1901–1971) was an Irish-born scientist (from Nenagh, County Tipperary), known for pioneering X-ray crystallography. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Hans Neurath (1909- 12 April 2002) was an early protein scientist. ... Maurice Loyal Huggins (19 September 1897- 17 December 1981) was a scientist who independently conceived the idea of hydrogen bonding and who was an early advocate for their role in stabilizing protein secondary structure. ... Linus Carl Pauling (February 28, 1901 – August 19, 1994) was an American quantum chemist and biochemist. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... John Desmond Bernal (1901–1971) was an Irish-born scientist (from Nenagh, County Tipperary), known for pioneering X-ray crystallography. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Dorothy Maud Wrinch (September 12, 1894 - February 11, 1976; married names Nicholson, Glaser) was a mathematician and biochemical theorist best known for her attempt to explain protein structure using mathematical principles. ... Abraham (Bram) Pais (May 19, 1918, Amsterdam, The Netherlands — July 28, 2000, Copenhagen, Denmark) was a Dutch-born American physicist and science historian. ... Niels (Henrik David) Bohr (October 7, 1885 – November 18, 1962) was a Danish physicist who made fundamental contributions to understanding atomic structure and quantum mechanics, for which he received the Nobel Prize in 1922. ... Niels (Henrik David) Bohr (October 7, 1885 – November 18, 1962) was a Danish physicist who made fundamental contributions to understanding atomic structure and quantum mechanics, for which he received the Nobel Prize in 1922. ... Niels (Henrik David) Bohr (October 7, 1885 – November 18, 1962) was a Danish physicist who made fundamental contributions to understanding atomic structure and quantum mechanics, for which he received the Nobel Prize in 1922. ... Niels (Henrik David) Bohr (October 7, 1885 – November 18, 1962) was a Danish physicist who made fundamental contributions to understanding atomic structure and quantum mechanics, for which he received the Nobel Prize in 1922. ... Linus Carl Pauling (February 28, 1901 – August 19, 1994) was an American quantum chemist and biochemist. ... Rosalind Elsie Franklin (25 July 1920 – 16 April 1958) was an English physical chemist and crystallographer who made important contributions to the understanding of the fine structures of DNA, viruses, coal and graphite. ... The joke funeral card in the names of Rosalind Franklin and Raymond Gosling Raymond Gosling is a distinguished scientist who worked with both Maurice Wilkins and Rosalind Franklin at Kings College London in deducing the structure of DNA. He was born in 1926 and attended school in Wembley. ... James Dewey Watson born April 6, 1928) is an American molecular biologist, best known as one of the co-discoverers of the structure of the DNA molecule. ... Francis Harry Compton Crick OM FRS (8 June 1916 – 28 July 2004) was an English molecular biologist, physicist, and neuroscientist, who is most noted for being one of the co-discoverers of the structure of the DNA molecule in 1953. ... Abraham (Bram) Pais (May 19, 1918, Amsterdam, The Netherlands — July 28, 2000, Copenhagen, Denmark) was a Dutch-born American physicist and science historian. ...

Further reading

• "Protein Units Put in Graphic 'Cage'," New York Times, 19 April 1940, page 14.

• "Waffle-Iron Theory of Proteins," New York Times, 2 February 1947, page E9.

• Structures of Matter and Patterns in Science, inspired by the work and life of Dorothy Wrinch, 1894–1976, Proceedings of a Symposium held at Smith College, Northampton, Massachusetts on 28–30 September 1977.

• Selected papers of Dorothy Wrinch, from the Sophia Smith Collection. Marjorie Senechal, editor. Schenkman Publishing Company, 1980.