Denaturation (biochemistry)

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The effects of temperature on enzyme activity. Top - increasing temperature increases the rate of reaction (Q10 coefficient). Middle - the fraction of folded and functional enzyme decreases above its denaturation temperature. Bottom - consequently, an enzyme's optimal rate of reaction is at an intermediate temperature. Q10 graphs.svg
The effects of temperature on enzyme activity. Top - increasing temperature increases the rate of reaction (Q10 coefficient). Middle - the fraction of folded and functional enzyme decreases above its denaturation temperature. Bottom - consequently, an enzyme's optimal rate of reaction is at an intermediate temperature.
IUPAC definition
Process of partial or total alteration of the native secondary, and/or tertiary, and/or quaternary structures of proteins or nucleic acids resulting in a loss of bioactivity.

Note 1: Modified from the definition given in ref. [1]

Contents

Note 2: Denaturation can occur when proteins and nucleic acids are subjected to elevated temperature or to extremes of pH, or to nonphysiological concentrations of salt, organic solvents, urea, or other chemical agents.

Note 3: An enzyme loses its catalytic activity when it is denaturized. [2]

Denaturation is a process in which proteins or nucleic acids lose the quaternary structure, tertiary structure, and secondary structure which is present in their native state, by application of some external stress or compound such as a strong acid or base, a concentrated inorganic salt, an organic solvent (e.g., alcohol or chloroform), radiation or heat. [3] If proteins in a living cell are denatured, this results in disruption of cell activity and possibly cell death. Protein denaturation is also a consequence of cell death. [4] [5] Denatured proteins can exhibit a wide range of characteristics, from conformational change and loss of solubility to aggregation due to the exposure of hydrophobic groups. Denatured proteins lose their 3D structure and therefore cannot function.

Protein biological molecule consisting of chains of amino acid residues

Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, 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 three-dimensional structure that determines its activity.

Nucleic acid polymeric macromolecules

Nucleic acids are the biopolymers, or small biomolecules, essential to all known forms of life. The term nucleic acid is the overall name for DNA and RNA. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. If the sugar is a compound ribose, the polymer is RNA ; if the sugar is derived from ribose as deoxyribose, the polymer is DNA.

In biochemistry, the native state of a protein or nucleic acid is its properly folded and/or assembled form, which is operative and functional. The native state of a biomolecule may possess all four levels of biomolecular structure, with the secondary through quaternary structure being formed from weak interactions along the covalently-bonded backbone. This is in contrast to the denatured state, in which these weak interactions are disrupted, leading to the loss of these forms of structure and retaining only the biomolecule's primary structure.

Protein folding is key to whether a globular or membrane protein can do its job correctly; it must be folded into the right shape to function. However, hydrogen bonds, which play a big part in folding, are rather weak and thus easily affected by heat, acidity, varying salt concentrations, and other stressors which can denature the protein. This is one reason why tight homeostasis is physiologically necessary in many life forms.

Protein folding the process of assisting in the covalent and noncovalent assembly of single chain polypeptides or multisubunit complexes into the correct tertiary structure

Protein folding is the physical process by which a protein chain acquires its native 3-dimensional structure, a conformation that is usually biologically functional, in an expeditious and reproducible manner. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil. Each protein exists as an unfolded polypeptide or random coil when translated from a sequence of mRNA to a linear chain of amino acids. This polypeptide lacks any stable (long-lasting) three-dimensional structure. As the polypeptide chain is being synthesized by a ribosome, the linear chain begins to fold into its three-dimensional structure. Folding begins to occur even during translation of the polypeptide chain. Amino acids interact with each other to produce a well-defined three-dimensional structure, the folded protein, known as the native state. The resulting three-dimensional structure is determined by the amino acid sequence or primary structure.

Globular protein spherical ("globe-like") protein; one of the common protein types (the others being fibrous, disordered and membrane proteins); somewhat water-soluble (forming colloids in water), unlike the fibrous or membrane proteins

Globular proteins or spheroproteins are spherical ("globe-like") proteins and are one of the common protein types. Globular proteins are somewhat water-soluble, unlike the fibrous or membrane proteins. There are multiple fold classes of globular proteins, since there are many different architectures that can fold into a roughly spherical shape.

Membrane protein class of proteins

Membrane proteins are proteins that interact with, or are part of, biological membranes. They include integral membrane proteins that are permanently anchored or part of the membrane and peripheral membrane proteins that are only temporarily attached to the lipid bilayer or to other integral proteins. The integral membrane proteins are classified as transmembrane proteins that span across the membrane and integral monotopic proteins that are attached to only one side of the membrane. Membrane proteins are a common type of proteins along with soluble globular proteins, fibrous proteins, and disordered proteins. They are targets of over 50% of all modern medicinal drugs. It is estimated that 20–30% of all genes in most genomes encode membrane proteins.

This concept is unrelated to denatured alcohol, which is alcohol that has been mixed with additives to make it unsuitable for human consumption.

Denatured alcohol ethanol with additives to discourage recreational consumption

Denatured alcohol, also called methylated spirit or denatured rectified spirit, is ethanol that has additives to make it poisonous, bad-tasting, foul-smelling, or nauseating to discourage recreational consumption. It is sometimes dyed. Pyridine, methanol, or both can be added to make denatured alcohol poisonous, and denatonium can be added to make it bitter.

Common examples

(Top) The protein albumin in the egg white undergoes denaturation and loss of solubility when the egg is cooked. (Bottom) Nitinol paperclips provide a visual analogy to help with the conceptualization of the denaturation process. Protein Denaturation.png
(Top) The protein albumin in the egg white undergoes denaturation and loss of solubility when the egg is cooked. (Bottom) Nitinol paperclips provide a visual analogy to help with the conceptualization of the denaturation process.

When food is cooked, some of its proteins become denatured. This is why boiled eggs become hard and cooked meat becomes firm.

A classic example of denaturing in proteins comes from egg whites, which are typically largely egg albumins in water. Fresh from the eggs, egg whites are transparent and liquid. Cooking the thermally unstable whites turns them opaque, forming an interconnected solid mass. [6] The same transformation can be effected with a denaturing chemical. Pouring egg whites into a beaker of acetone will also turn egg whites translucent and solid. The skin that forms on curdled milk is another common example of denatured protein. The cold appetizer known as ceviche is prepared by chemically "cooking" raw fish and shellfish in an acidic citrus marinade, without heat. [7]

Ovalbumin protein

Ovalbumin is the main protein found in egg white, making up approximately 55% of the total protein. Ovalbumin displays sequence and three-dimensional homology to the serpin superfamily, but unlike most serpins it is not a serine protease inhibitor. The function of ovalbumin is unknown, although it is presumed to be a storage protein.

Thermostability

Thermostability is the quality of a substance to resist irreversible change in its chemical or physical structure, often by resisting decomposition or polymerization, at a high relative temperature.

Acetone chemical compound

Acetone, or propanone, is the organic compound with the formula (CH3)2CO. It is a colorless, volatile, flammable liquid and is the simplest and smallest ketone.

Protein denaturation

Denatured proteins can exhibit a wide range of characteristics, from loss of solubility to protein aggregation.

Solubility Capacity of a designated solvent to hold a designated solute in homogeneous solution under specified conditions

Solubility is the property of a solid, liquid or gaseous chemical substance called solute to dissolve in a solid, liquid or gaseous solvent. The solubility of a substance fundamentally depends on the physical and chemical properties of the solute and solvent as well as on temperature, pressure and presence of other chemicals of the solution. The extent of the solubility of a substance in a specific solvent is measured as the saturation concentration, where adding more solute does not increase the concentration of the solution and begins to precipitate the excess amount of solute.

Protein aggregation

Protein aggregation is a biological phenomenon in which mis-folded proteins aggregate either intra- or extracellularly. These protein aggregates are often correlated with diseases. In fact, protein aggregates have been implicated in a wide variety of disease known as amyloidoses, including ALS, Alzheimer's, Parkinson's and prion disease.

Functional proteins have four levels of structural organization:
1) Primary Structure : the linear structure of amino acids in the polypeptide chain
2) Secondary Structure : hydrogen bonds between peptide group chains in an alpha helix or beta sheet
3) Tertiary Structure : three-dimensional structure of alpha helixes and beta helixes folded
4) Quaternary Structure : three-dimensional structure of multiple polypeptides and how they fit together Levels of structural organization of a protein.svg
Functional proteins have four levels of structural organization:
1) Primary Structure : the linear structure of amino acids in the polypeptide chain
2) Secondary Structure : hydrogen bonds between peptide group chains in an alpha helix or beta sheet
3) Tertiary Structure : three-dimensional structure of alpha helixes and beta helixes folded
4) Quaternary Structure : three-dimensional structure of multiple polypeptides and how they fit together
Process of Denaturation: 1) Functional protein showing a quaternary structure 2) when heat is applied it alters the intramolecular bonds of the protein 3) unfolding of the polypeptides (amino acids) Process of Denaturation.svg
Process of Denaturation: 1) Functional protein showing a quaternary structure 2) when heat is applied it alters the intramolecular bonds of the protein 3) unfolding of the polypeptides (amino acids)

Background

Proteins or Polypeptides are polymers of amino acids. A protein is created by ribosomes that "read" RNA that is encoded by codons in the gene and assemble the requisite amino acid combination from the genetic instruction, in a process known as translation. The newly created protein strand then undergoes posttranslational modification, in which additional atoms or molecules are added, for example copper, zinc, or iron. Once this post-translational modification process has been completed, the protein begins to fold (sometimes spontaneously and sometimes with enzymatic assistance), curling up on itself so that hydrophobic elements of the protein are buried deep inside the structure and hydrophilic elements end up on the outside. The final shape of a protein determines how it interacts with its environment.

Protein folding consists of a balance between a substantial amount of weak intra-molecular interactions within a protein (Hydrophobic, electrostatic, and Van Der Waals Interactions) and protein-solvent interactions. [8] As a result, this process is heavily reliant on environmental state that the protein resides in. [8] These environmental conditions include, and are not limited to, temperature, salinity, pressure, and the solvents that happen to be involved. [8] Consequently, any exposure to extreme stresses (e.g. heat or radiation, high inorganic salt concentrations, strong acids and bases) can disrupt a protein's interaction and inevitably lead to denaturation. [9]

When a protein is denatured, secondary and tertiary structures are altered but the peptide bonds of the primary structure between the amino acids are left intact. Since all structural levels of the protein determine its function, the protein can no longer perform its function once it has been denatured. This is in contrast to intrinsically unstructured proteins, which are unfolded in their native state, but still functionally active and tend to fold upon binding to their biological target. [10]

How denaturation occurs at levels of protein structure

Loss of function

Most biological substrates lose their biological function when denatured. For example, enzymes lose their activity, because the substrates can no longer bind to the active site, and because amino acid residues involved in stabilizing substrates' transition states are no longer positioned to be able to do so. The denaturing process and the associated loss of activity can be measured using techniques such as dual polarization interferometry, CD, QCM-D and MP-SPR.

Loss of activity due to heavy metals and metalloids

By targeting proteins, heavy metals have been known to disrupt the function and activity carried out by proteins. [12] It is important to note that heavy metals fall into categories consisting of transition metals as well as a select amount of metalloid. [12] These metals, when interacting with native, folded proteins, tend to play a role in obstructing their biological activity. [12] This interference can be carried out in a different number of ways. These heavy metals can form a complex with the functional side chain groups present in a protein or form bonds to free thiols. [12] Heavy metals also play a role in oxidizing amino acid side chains present in protein. [12] Along with this, when interacting with metalloproteins, heavy metals can dislocate and replace key metal ions. [12] As a result, heavy metals can interfere with folded proteins, which can strongly deter protein stability and activity.

Reversibility and irreversibility

In many cases, denaturation is reversible (the proteins can regain their native state when the denaturing influence is removed). This process can be called renaturation. [13] This understanding has led to the notion that all the information needed for proteins to assume their native state was encoded in the primary structure of the protein, and hence in the DNA that codes for the protein, the so-called "Anfinsen's thermodynamic hypothesis". [14]

Denaturation can also be irreversible. This irreversibility is typically a kinetic, not thermodynamic irreversibility, as generally when a protein is folded it has lower free energy. Through kinetic irreversibility, the fact that the protein is stuck in a local minimum can stop it from ever refolding after it has been irreversibly denatured. [15]

Protein denaturation due to pH

Denaturation can also be caused by changes in the pH which can affect the chemistry of the amino acids and their residues. The ionizable groups in amino acids are able to become ionized when changes in pH occur. A pH change to more acidic or more basic conditions can induce unfolding. [16] Acid-induced unfolding often occurs between pH 2 and 5, base-induced unfolding usually requires pH 10 or higher. [16]

Nucleic acid denaturation

Nucleic acids (including RNA and DNA) are nucleotide polymers synthesized by polymerase enzymes during either transcription or DNA replication. Following 5'-3' synthesis of the backbone, individual nitrogenous bases are capable of interacting with one another via hydrogen bonding, thus allowing for the formation of higher-order structures. Nucleic acid denaturation occurs when hydrogen bonding between nucleotides is disrupted, and results in the separation of previously annealed strands. For example, denaturation of DNA due to high temperatures results in the disruption of Watson and Crick base pairs and the separation of the double stranded helix into two single strands. Nucleic acid strands are capable of re-annealling when "normal" conditions are restored, but if restoration occurs too quickly, the nucleic acid strands may re-anneal imperfectly resulting in the improper pairing of bases.

Biologically-induced denaturation

DNA denaturation occurs when hydrogen bonds between Watson and Crick base pairs are disturbed. DNA Denaturation.png
DNA denaturation occurs when hydrogen bonds between Watson and Crick base pairs are disturbed.

The non-covalent interactions between antiparallel strands in DNA can be broken in order to "open" the double helix when biologically important mechanisms such as DNA replication, transcription, DNA repair or protein binding are set to occur. [17] The area of partially separated DNA is known as the denaturation bubble, which can be more specifically defined as the opening of a DNA double helix through the coordinated separation of base pairs. [17]

The first model that attempted to describe the thermodynamics of the denaturation bubble was introduced in 1966 and called the Poland-Scheraga Model. This model describes the denaturation of DNA strands as a function of temperature. As the temperature increases, the hydrogen bonds between the Watson and Crick base pairs are increasingly disturbed and "denatured loops" begin to form. [18] However, the Poland-Scheraga Model is now considered elementary because it fails to account for the confounding implications of DNA sequence, chemical composition, stiffness and torsion. [19]

Recent thermodynamic studies have inferred that the lifetime of a singular denaturation bubble ranges from 1 microsecond to 1 millisecond. [20] This information is based on established timescales of DNA replication and transcription. [20] Currently,[ when? ] biophysical and biochemical research studies are being performed to more fully elucidate the thermodynamic details of the denaturation bubble. [20]

Denaturation due to chemical agents

Formamide denatures DNA by disrupting the hydrogen bonds between Watson and Crick base pairs. Orange, blue, green, and purple lines represent adenine, thymine, guanine, and cytosine respectively. The three short black lines between the bases and the formamide molecules represent newly formed hydrogen bonds. DNA Denaturation by Formamide.png
Formamide denatures DNA by disrupting the hydrogen bonds between Watson and Crick base pairs. Orange, blue, green, and purple lines represent adenine, thymine, guanine, and cytosine respectively. The three short black lines between the bases and the formamide molecules represent newly formed hydrogen bonds.

With polymerase chain reaction (PCR) being among the most popular contexts in which DNA denaturation is desired, heating is the most frequent method of denaturation. [21] Other than denaturation by heat, nucleic acids can undergo the denaturation process through various chemical agents such as formamide, guanidine, sodium salicylate, dimethyl sulfoxide (DMSO), propylene glycol, and urea. [22] These chemical denaturing agents lower the melting temperature (Tm) by competing for hydrogen bond donors and acceptors with pre-existing nitrogenous base pairs. Some agents are even able to induce denaturation at room temperature. For example, alkaline agents (e.g. NaOH) have been shown to denature DNA by changing pH and removing hydrogen-bond contributing protons. [21] These denaturants have been employed to make Denaturing Gradient Gel Electrophoresis gel (DGGE), which promotes denaturation of nucleic acids in order to eliminate the influence of nucleic acid shape on their electrophoretic mobility. [23]

Chemical denaturation as an alternative

The optical activity (absorption and scattering of light) and hydrodynamic properties (translational diffusion, sedimentation coefficients, and rotational correlation times) of formamide denatured nucleic acids are similar to those of heat-denatured nucleic acids. [22] [24] [25] Therefore, depending on the desired effect, chemically denaturing DNA can provide a gentler procedure for denaturing nucleic acids than denaturation induced by heat. Studies comparing different denaturation methods such as heating, beads mill of different bead sizes, probe sonification, and chemical denaturation show that chemical denaturation can provide quicker denaturation compared to the other physical denaturation methods described. [21] Particularly in cases where rapid renaturation is desired, chemical denaturation agents can provide an ideal alternative to heating. For example, DNA strands denatured with alkaline agents such as NaOH renature as soon as phosphate buffer is added. [21]

Denaturation due to air

Small, electronegative molecules such as nitrogen and oxygen, which are the primary gases in air, significantly impact the ability of surrounding molecules to participate in hydrogen bonding. [26] These molecules compete with surrounding hydrogen bond acceptors for hydrogen bond donors, therefore acting as "hydrogen bond breakers" and weakening interactions between surrounding molecules in the environment. [26] Antiparellel strands in DNA double helices are non-covalently bound by hydrogen bonding between Watson and Crick base pairs; [27] nitrogen and oxygen therefore maintain the potential to weaken the integrity of DNA when exposed to air. [28] As a result, DNA strands exposed to air require less force to separate and exemplify lower melting temperatures. [28]

Applications

Many laboratory techniques rely on the ability of nucleic acid strands to separate. By understanding the properties of nucleic acid denaturation, the following methods were created:

Denaturants

Protein Denaturants

Acids

Acidic protein denaturants include:

Bases

Bases work similarly to acids in denaturation. They include:

Solvents

Most organic solvents are denaturing, including:[ citation needed ]

Cross-linking reagents

Cross-linking agents for proteins include:[ citation needed ]

Chaotropic agents

Chaotropic agents include:[ citation needed ]

Disulfide bond reducers

Agents that break disulfide bonds by reduction include:[ citation needed ]

Other

Nucleic Acid Denaturants

Chemical

Acidic nucleic acid denaturants include:

Basic nucleic acid denaturants include:

  • NaOH

Other nucleic acid denaturants include:

Physical

See also

Related Research Articles

Alpha helix type of secondary structure

The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group donates a hydrogen bond to the backbone C=O group of the amino acid located three or four residues earlier along the protein sequence.

Base pair unit consisting of two nucleobases bound to each other by hydrogen bonds: either adenine–thymine or guanine–cytosine in natural DNA (additional types occur in RNA)

A base pair (bp) is a unit consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA and RNA. Dictated by specific hydrogen bonding patterns, Watson-Crick base pairs allow the DNA helix to maintain a regular helical structure that is subtly dependent on its nucleotide sequence. The complementary nature of this based-paired structure provides a redundant copy of the genetic information encoded within each strand of DNA. The regular structure and data redundancy provided by the DNA double helix make DNA well suited to the storage of genetic information, while base-pairing between DNA and incoming nucleotides provides the mechanism through which DNA polymerase replicates DNA and RNA polymerase transcribes DNA into RNA. Many DNA-binding proteins can recognize specific base-pairing patterns that identify particular regulatory regions of genes.

Hydrogen bond form of association between an electronegative atom and a hydrogen atom attached to a second,relatively electronegative atom;electrostatic interaction,heightened by the small size of hydrogen which permits proximity of the interacting dipoles/charges

A hydrogen bond is a partially electrostatic force of attraction between a hydrogen (H) atom which is bound to a more electronegative atom or group, such as nitrogen (N), oxygen (O), or fluorine (F)—the hydrogen bond donor—and another adjacent atom bearing a lone pair of electrons—the hydrogen bond acceptor. Weak hydrogen bonds occur even with C-H groups as donor

Protein secondary structure general three-dimensional form of local segments of proteins

Protein secondary structure is the three dimensional form of local segments of proteins. The two most common secondary structural elements are alpha helices and beta sheets, though beta turns and omega loops occur as well. Secondary structure elements typically spontaneously form as an intermediate before the protein folds into its three dimensional tertiary structure.

Biomolecule molecule that is produced by a living organism

A biomolecule or biological molecule is a loosely used term for molecules and ions that are present in organisms, essential to some typically biological process such as cell division, morphogenesis, or development. Biomolecules include large macromolecules such as proteins, carbohydrates, lipids, and nucleic acids, as well as small molecules such as primary metabolites, secondary metabolites, and natural products. A more general name for this class of material is biological materials. Biomolecules are usually endogenous but may also be exogenous. For example, pharmaceutical drugs may be natural products or semisynthetic (biopharmaceuticals) or they may be totally synthetic.

Salting out is an effect based on the electrolyte-non electrolyte interaction, in which the non-electrolyte could be less soluble at high salt concentrations. It is used as a method of purification for proteins, as well as preventing protein denaturation due to excessively diluted samples during experiments. The salt concentration needed for the protein to precipitate out of the solution differs from protein to protein. This process is also used to concentrate dilute solutions of proteins. Dialysis can be used to remove the salt if needed.

Protein structure three-dimensional arrangement of atoms in an amino acid-chain molecule

Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers – specifically polypeptides – formed from sequences of amino acids, the monomers of the polymer. A single amino acid monomer may also be called a residue indicating a repeating unit of a polymer. Proteins form by amino acids undergoing condensation reactions, in which the amino acids lose one water molecule per reaction in order to attach to one another with a peptide bond. By convention, a chain under 30 amino acids is often identified as a peptide, rather than a protein. To be able to perform their biological function, proteins fold into one or more specific spatial conformations driven by a number of non-covalent interactions such as hydrogen bonding, ionic interactions, Van der Waals forces, and hydrophobic packing. To understand the functions of proteins at a molecular level, it is often necessary to determine their three-dimensional structure. This is the topic of the scientific field of structural biology, which employs techniques such as X-ray crystallography, NMR spectroscopy, and dual polarisation interferometry to determine the structure of proteins.

A chaotropic agent is a molecule in water solution that can disrupt the hydrogen bonding network between water molecules. This has an effect on the stability of the native state of other molecules in the solution, mainly macromolecules by weakening the hydrophobic effect. For example, a chaotropic agent reduces the amount of order in the structure of a protein formed by water molecules, both in the bulk and the hydration shells around hydrophobic amino acids, and may cause its denaturation.

Hydrophobic effect

The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in an aqueous solution and exclude water molecules. The word hydrophobic literally means "water-fearing", and it describes the segregation of water and nonpolar substances, which maximizes hydrogen bonding between molecules of water and minimizes the area of contact between water and nonpolar molecules.

A non-covalent interaction differs from a covalent bond in that it does not involve the sharing of electrons, but rather involves more dispersed variations of electromagnetic interactions between molecules or within a molecule. The chemical energy released in the formation of non-covalent interactions is typically on the order of 1-5 kcal/mol. Non-covalent interactions can be classified into different categories, such as electrostatic, π-effects, van der Waals forces, and hydrophobic effects.

Biomolecular structure 3D conformation of a biological sequence, like DNA, RNA, proteins

Biomolecular structure is the intricate folded, three-dimensional shape that is formed by a molecule of protein, DNA, or RNA, and that is important to its function. The structure of these molecules may be considered at any of several length scales ranging from the level of individual atoms to the relationships among entire protein subunits. This useful distinction among scales is often expressed as a decomposition of molecular structure into four levels: primary, secondary, tertiary, and quaternary. The scaffold for this multiscale organization of the molecule arises at the secondary level, where the fundamental structural elements are the molecule's various hydrogen bonds. This leads to several recognizable domains of protein structure and nucleic acid structure, including such secondary-structure features as alpha helixes and beta sheets for proteins, and hairpin loops, bulges, and internal loops for nucleic acids. The terms primary, secondary, tertiary, and quaternary structure were introduced by Kaj Ulrik Linderstrøm-Lang in his 1951 Lane Medical Lectures at Stanford University.

Hyperchromicity

Hyperchromicity is the increase of absorbance of a material. The most famous example is the hyperchromicity of DNA that occurs when the DNA duplex is denatured. The UV absorption is increased when the two single DNA strands are being separated, either by heat or by addition of denaturant or by increasing the pH level. The opposite, a decrease of absorbance is called hypochromicity.

Cyclol

The cyclol hypothesis is the first structural model of a folded, globular protein. 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 ; 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 and cyclol fabrics. 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.

Nucleic acid thermodynamics is the study of how temperature affects the nucleic acid structure of double-stranded DNA (dsDNA). The melting temperature (Tm) is defined as the temperature at which half of the DNA strands are in the random coil or single-stranded (ssDNA) state. Tm depends on the length of the DNA molecule and its specific nucleotide sequence. DNA, when in a state where its two strands are dissociated, is referred to as having been denatured by the high temperature.

Nucleic acid structure organization of DNA and RNA molecules at different scales

Nucleic acid structure refers to the structure of nucleic acids such as DNA and RNA. Chemically speaking, DNA and RNA are very similar. Nucleic acid structure is often divided into four different levels: primary, secondary, tertiary and quaternary.

Nucleic acid secondary structure basepairing interactions within a single nucleic acid polymer or between two polymers, list of bases which are paired in a nucleic acid molecule

Nucleic acid secondary structure is the basepairing interactions within a single nucleic acid polymer or between two polymers. It can be represented as a list of bases which are paired in a nucleic acid molecule. The secondary structures of biological DNA's and RNA's tend to be different: biological DNA mostly exists as fully base paired double helices, while biological RNA is single stranded and often forms complex and intricate base-pairing interactions due to its increased ability to form hydrogen bonds stemming from the extra hydroxyl group in the ribose sugar.

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