Molecular models of DNA
Encyclopedia
Molecular models of DNA structures are representations of the molecular geometry
and topology of Deoxyribonucleic acid (DNA
) molecules using one of several means, with the aim of simplifying and presenting the essential, physical and chemical, properties of DNA molecular structures either in vivo or in vitro. These representations include closely packed spheres (CPK
models) made of plastic, metal wires for 'skeletal models', graphic computations and animations by computers, artistic rendering. Computer molecular models also allow animations and molecular dynamics simulations that are very important for understanding how DNA functions in vivo.
The more advanced, computer-based molecular model
s of DNA involve molecular dynamics
simulations as well as quantum mechanical
computations of vibro-rotations, delocalized molecular orbital
s (MOs), electric dipole moment
s, hydrogen-bonding, and so on. DNA molecular dynamics modeling involves simulations of DNA
molecular geometry
and topology changes with time as a result of both intra- and inter- molecular interactions of DNA. Whereas molecular models of Deoxyribonucleic acid (DNA
) molecules such as closely packed spheres (CPK
models) made of plastic or metal wires for 'skeletal models' are useful representations of static DNA structures, their usefulness is very limited for representing complex DNA dynamics. Computer molecular modeling allows both animations and molecular dynamics simulations that are very important for understanding how DNA functions in vivo
.
From the very early stages of structural studies of DNA by X-ray diffraction and biochemical means, molecular models such as the Watson-Crick double-helix model were successfully employed to solve the 'puzzle' of DNA structure, and also find how the latter relates to its key functions in living cells. The first high quality X-ray diffraction patterns
of A-DNA were reported by Rosalind Franklin
and Raymond Gosling
in 1953. The first calculations of the Fourier transform of an atomic helix were reported one year earlier by Cochran, Crick and Vand, and were followed in 1953 by the computation of the Fourier transform of a coiled-coil by Crick.
Structural information is generated from X-ray diffraction studies of oriented DNA fibers with the help of molecular models of DNA that are combined with crystallographic and mathematical analysis of the X-ray patterns.
The first reports of a double-helix molecular model of B-DNA structure were made by Watson and Crick in 1953. Last-but-not-least, Maurice F. Wilkins,
A. Stokes and H.R. Wilson, reported the first X-ray patterns
of in vivo B-DNA in partially oriented salmon sperm heads.
The development of the first correct double-helix molecular model of DNA by Crick and Watson may not have been possible without the biochemical evidence for the nucleotide base-pairing ([A---T]; [C---G]), or Chargaff's rules
.Although such initial studies of DNA structures with the help of molecular models were essentially static, their consequences for explaining the in vivo functions of DNA were significant in the areas of protein biosynthesis and the quasi-universality of the genetic code. Epigenetic transformation studies of DNA in vivo were however much slower to develop in spite of their importance for embryology, morphogenesis and cancer research. Such chemical dynamics and biochemical reactions of DNA are much more complex than the molecular dynamics of DNA physical interactions with water, ions and proteins/enzymes in living cells.
units of four basic types, attached to deoxyribose and phosphate groups), its molecular structure in vivo undergoes dynamic configuration changes that involve dynamically attached water molecules and ions. Supercoiling, packing with histones in chromosome structures, and other such supramolecular aspects also involve in vivo DNA topology which is even more complex than DNA molecular geometry, thus turning molecular modeling of DNA into an especially challenging problem for both molecular biologists and biotechnologists. Like other large molecules and biopolymers, DNA often exists in multiple stable geometries (that is, it exhibits conformational isomerism
) and configurational, quantum states which are close to each other in energy on the potential energy surface of the DNA molecule.
Such varying molecular geometries can also be computed, at least in principle, by employing ab initio quantum chemistry
methods that can attain high accuracy for small molecules, although claims that acceptable accuracy can be also achieved for polynuclelotides, as well as DNA conformations, were recently made on the basis of VCD
spectral data. Such quantum geometries define an important class of ab initio molecular models of DNA whose exploration has barely started especially in connection with results obtained by VCD in solutions. More detailed comparisons with such ab initio quantum computations are in principle obtainable through 2D-FT NMR spectroscopy and relaxation studies of polynucleotide solutions or specifically labeled DNA, as for example with deuterium labels.
In an interesting twist of roles, the DNA molecule itself was proposed to be utilized for quantum computing
. Both DNA nanostructures as well as DNA 'computing' biochips have been built.
The chemical structure of DNA is insufficient to understand the complexity of the 3D structures of DNA. On the other hand, animated molecular models allow one to visually explore the three-dimensional (3D) structure of DNA. The DNA model shown (far right) is a space-filling, or CPK
, model of the DNA double-helix. Animated molecular models, such as the wire, or skeletal, type shown at the top of this article, allow one to visually explore the three-dimensional (3D) structure of DNA. Another type of DNA model is the space-filling, or CPK
, model.
The hydrogen bonding dynamics and proton exchange is very different by many orders of magnitude between the two systems of fully hydrated DNA and water molecules in ice. Thus, the DNA dynamics is complex, involving nanosecond and several tens of picosecond time scales, whereas that of liquid ice is on the picosecond time scale, and that of proton exchange in ice is on the millisecond time scale. The proton exchange rates in DNA and attached proteins may vary from picosecond to nanosecond, minutes or years, depending on the exact locations of the exchanged protons in the large biopolymers.
A simple harmonic oscillator
'vibration' is only an oversimplified dynamic representation of the longitudinal vibrations of the DNA intertwined helices which were found to be anharmonic
rather than harmonic as often assumed in quantum dynamic simulations
of DNA.
shows a variety of forms, both double-stranded and single-stranded. The mechanical properties of DNA, which are directly related to its structure, are a significant problem for cells
. Every process which binds or reads DNA
is able to use or modify the mechanical properties of DNA for purposes of recognition, packaging and modification. The extreme length (a chromosome
may contain a 10 cm long DNA strand), relative rigidity and helical structure of DNA has led to the evolution
of histone
s and of enzyme
s such as topoisomerase
s and helicase
s to manage a cell's DNA. The properties of DNA are closely related to its molecular structure and sequence, particularly the weakness of the hydrogen bonds and electronic interactions that hold strands of DNA together compared to the strength of the bonds within each strand.
Experimental techniques which can directly measure the mechanical properties of DNA are relatively new, and high-resolution visualization in solution is often difficult. Nevertheless, scientists have uncovered large amount of data on the mechanical properties of this polymer, and the implications of DNA's mechanical properties on cellular processes is a topic of active current research.
The DNA found in many cells can be macroscopic in length - a few centimetres long for each human chromosome. Consequently, cells must compact or "package" DNA to carry it within them. In eukaryote
s this is carried by spool-like protein
s known as histone
s, around which DNA winds. It is the further compaction of this DNA-protein complex which produces the well known mitotic eukaryotic chromosome
s.
Alternate non-double-helical models have been proposed for the in vivo structure of DNA, such as in plasmid
s and chromatin
. Such "side-by-side" models of DNA were proposed early in the history of molecular biology
, but these were set aside in favor of the double-helical model due to X-ray crystallography
of DNA duplexes and later the nucleosome core particle, as well as the discovery of topoisomerases, and these non-double-helical models are not currently accepted by the mainstream scientific community.
After DNA has been separated and purified by standard biochemical techniques one has a sample in a jar much like in the figure at the top of this article. Below are the main steps involved in generating structural information from X-ray diffraction studies of oriented DNA fibers that are drawn from the hydrated DNA sample with the help of molecular models of DNA that are combined with crystallographic and mathematical analysis of the X-ray patterns.
A paracrystalline lattice
, or paracrystal, is a molecular or atomic lattice with significant amounts (e.g., larger than a few percent) of partial disordering of molecular arrangements. Limiting cases of the paracrystal model are nanostructure
s, such as glass
es, liquid
s, etc., that may possess only local ordering and no global order. A simple example of a paracrystalline lattice is shown in the following figure for a silica glass:
Liquid crystal
s also have paracrystalline rather than crystal
line structures.
Highly hydrated B-DNA occurs naturally in living cells in such a paracrystalline state, which is a dynamic one in spite of the relatively rigid DNA double-helix stabilized by parallel hydrogen bonds between the nucleotide base-pairs in the two complementary, helical DNA chains (see figures). For simplicity most DNA molecular models omit both water and ions dynamically bound to B-DNA, and are thus less useful for understanding the dynamic behaviors of B-DNA in vivo. The physical and mathematical analysis of X-ray and spectroscopic data for paracrystalline B-DNA is therefore much more complicated than that of crystalline, A-DNA X-ray diffraction patterns. The paracrystal model is also important for DNA technological applications such as DNA nanotechnology
. Novel techniques that combine X-ray diffraction of DNA with X-ray microscopy in hydrated living cells are now also being developed.
There are various uses of DNA molecular modeling in Genomics and Biotechnology research applications, from DNA repair to PCR and DNA nanostructures
. Two-dimensional DNA junction arrays have been visualized by Atomic force microscopy.
DNA molecular modeling has various uses in genomics
and biotechnology
, with research applications ranging from DNA repair to PCR and DNA nanostructures. These include computer molecular models of molecules as varied as RNA polymerase, an E. coli, bacterial DNA primase template suggesting very complex dynamics at the interfaces between the enzymes and the DNA template, and molecular models of the mutagenic, chemical interaction of potent carcinogen molecules with DNA. These are all represented in the gallery below.
Technological application include a DNA biochip and DNA nanostructures designed for DNA computing
and other dynamic applications of DNA nanotechnology
.
The image at right is of self-assembled DNA nanostructures. The DNA “tile” structure in this image consists of four branched junctions oriented at 90° angles. Each tile consists of nine DNA oligonucleotides as shown; such tiles serve as the primary “building block” for the assembly of the DNA nanogrids shown in the AFM micrograph.
Quadruplex DNA may be involved in certain cancers. Images of quadruplex DNA are in the gallery below.
Neutron scattering
X-ray microscopy
Electron microscopy
NMR databases
Genomic and structural databases
Atomic force microscopy
Molecular geometry
Molecular geometry or molecular structure is the three-dimensional arrangement of the atoms that constitute a molecule. It determines several properties of a substance including its reactivity, polarity, phase of matter, color, magnetism, and biological activity.- Molecular geometry determination...
and topology of Deoxyribonucleic acid (DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
) molecules using one of several means, with the aim of simplifying and presenting the essential, physical and chemical, properties of DNA molecular structures either in vivo or in vitro. These representations include closely packed spheres (CPK
CPK
CPK may refer to:*Cpk, a measure of process capability*CPK coloring, a way to color atoms when visualizing molecular models*"C.P.K." , a 1995 song by Unwritten Law from their album Blue Room*Cabbage Patch Kids*California Pizza Kitchen...
models) made of plastic, metal wires for 'skeletal models', graphic computations and animations by computers, artistic rendering. Computer molecular models also allow animations and molecular dynamics simulations that are very important for understanding how DNA functions in vivo.
The more advanced, computer-based molecular model
Molecular model
A molecular model, in this article, is a physical model that represents molecules and their processes. The creation of mathematical models of molecular properties and behaviour is molecular modelling, and their graphical depiction is molecular graphics, but these topics are closely linked and each...
s of DNA involve molecular dynamics
Molecular dynamics
Molecular dynamics is a computer simulation of physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a period of time, giving a view of the motion of the atoms...
simulations as well as quantum mechanical
Quantum mechanics
Quantum mechanics, also known as quantum physics or quantum theory, is a branch of physics providing a mathematical description of much of the dual particle-like and wave-like behavior and interactions of energy and matter. It departs from classical mechanics primarily at the atomic and subatomic...
computations of vibro-rotations, delocalized molecular orbital
Molecular orbital
In chemistry, a molecular orbital is a mathematical function describing the wave-like behavior of an electron in a molecule. This function can be used to calculate chemical and physical properties such as the probability of finding an electron in any specific region. The term "orbital" was first...
s (MOs), electric dipole moment
Electric dipole moment
In physics, the electric dipole moment is a measure of the separation of positive and negative electrical charges in a system of charges, that is, a measure of the charge system's overall polarity with SI units of Coulomb-meter...
s, hydrogen-bonding, and so on. DNA molecular dynamics modeling involves simulations of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
molecular geometry
Molecular geometry
Molecular geometry or molecular structure is the three-dimensional arrangement of the atoms that constitute a molecule. It determines several properties of a substance including its reactivity, polarity, phase of matter, color, magnetism, and biological activity.- Molecular geometry determination...
and topology changes with time as a result of both intra- and inter- molecular interactions of DNA. Whereas molecular models of Deoxyribonucleic acid (DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
) molecules such as closely packed spheres (CPK
CPK
CPK may refer to:*Cpk, a measure of process capability*CPK coloring, a way to color atoms when visualizing molecular models*"C.P.K." , a 1995 song by Unwritten Law from their album Blue Room*Cabbage Patch Kids*California Pizza Kitchen...
models) made of plastic or metal wires for 'skeletal models' are useful representations of static DNA structures, their usefulness is very limited for representing complex DNA dynamics. Computer molecular modeling allows both animations and molecular dynamics simulations that are very important for understanding how DNA functions in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
.
History
of A-DNA were reported by Rosalind Franklin
Rosalind Franklin
Rosalind Elsie Franklin was a British biophysicist and X-ray crystallographer who made critical contributions to the understanding of the fine molecular structures of DNA, RNA, viruses, coal and graphite...
and Raymond Gosling
Raymond Gosling
Raymond Gosling is a distinguished scientist who worked with both Maurice Wilkins and Rosalind Franklin at King's College London in deducing the structure of DNA, under the direction of Sir John Randall. His other KCL colleagues included Alex Stokes and Herbert Wilson.-Early years:He was born in...
in 1953. The first calculations of the Fourier transform of an atomic helix were reported one year earlier by Cochran, Crick and Vand, and were followed in 1953 by the computation of the Fourier transform of a coiled-coil by Crick.
Structural information is generated from X-ray diffraction studies of oriented DNA fibers with the help of molecular models of DNA that are combined with crystallographic and mathematical analysis of the X-ray patterns.
The first reports of a double-helix molecular model of B-DNA structure were made by Watson and Crick in 1953. Last-but-not-least, Maurice F. Wilkins,
A. Stokes and H.R. Wilson, reported the first X-ray patterns
of in vivo B-DNA in partially oriented salmon sperm heads.
The development of the first correct double-helix molecular model of DNA by Crick and Watson may not have been possible without the biochemical evidence for the nucleotide base-pairing ([A---T]; [C---G]), or Chargaff's rules
Chargaff's rules
Chargaff's rules state that DNA from any cell of all organisms should have a 1:1 ratio of pyrimidine and purine bases and, more specifically, that the amount of guanine is equal to cytosine and the amount of adenine is equal to thymine. This pattern is found in both strands of the DNA...
.Although such initial studies of DNA structures with the help of molecular models were essentially static, their consequences for explaining the in vivo functions of DNA were significant in the areas of protein biosynthesis and the quasi-universality of the genetic code. Epigenetic transformation studies of DNA in vivo were however much slower to develop in spite of their importance for embryology, morphogenesis and cancer research. Such chemical dynamics and biochemical reactions of DNA are much more complex than the molecular dynamics of DNA physical interactions with water, ions and proteins/enzymes in living cells.
Importance
An old standing dynamic problem is how DNA "self-replication" takes place in living cells that should involve transient uncoiling of supercoiled DNA fibers. Although DNA consists of relatively rigid, very large elongated biopolymer molecules called "fibers" or chains (that are made of repeating nucleotideNucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
units of four basic types, attached to deoxyribose and phosphate groups), its molecular structure in vivo undergoes dynamic configuration changes that involve dynamically attached water molecules and ions. Supercoiling, packing with histones in chromosome structures, and other such supramolecular aspects also involve in vivo DNA topology which is even more complex than DNA molecular geometry, thus turning molecular modeling of DNA into an especially challenging problem for both molecular biologists and biotechnologists. Like other large molecules and biopolymers, DNA often exists in multiple stable geometries (that is, it exhibits conformational isomerism
Conformational isomerism
In chemistry, conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted exclusively by rotations about formally single bonds...
) and configurational, quantum states which are close to each other in energy on the potential energy surface of the DNA molecule.
Such varying molecular geometries can also be computed, at least in principle, by employing ab initio quantum chemistry
Quantum chemistry
Quantum chemistry is a branch of chemistry whose primary focus is the application of quantum mechanics in physical models and experiments of chemical systems...
methods that can attain high accuracy for small molecules, although claims that acceptable accuracy can be also achieved for polynuclelotides, as well as DNA conformations, were recently made on the basis of VCD
VCD
VCD is a three-letter abbreviation with multiple meanings, as described below:* VCD Athletic, semi-professional football team* Video CD* Voice command device* Value change dump * Vocal cord dysfunction* Visual Communication and Design...
spectral data. Such quantum geometries define an important class of ab initio molecular models of DNA whose exploration has barely started especially in connection with results obtained by VCD in solutions. More detailed comparisons with such ab initio quantum computations are in principle obtainable through 2D-FT NMR spectroscopy and relaxation studies of polynucleotide solutions or specifically labeled DNA, as for example with deuterium labels.
In an interesting twist of roles, the DNA molecule itself was proposed to be utilized for quantum computing
DNA computing
DNA computing is a form of computing which uses DNA, biochemistry and molecular biology, instead of the traditional silicon-based computer technologies. DNA computing, or, more generally, biomolecular computing, is a fast developing interdisciplinary area...
. Both DNA nanostructures as well as DNA 'computing' biochips have been built.
Fundamental concepts
The chemical structure of DNA is insufficient to understand the complexity of the 3D structures of DNA. On the other hand, animated molecular models allow one to visually explore the three-dimensional (3D) structure of DNA. The DNA model shown (far right) is a space-filling, or CPK
CPK
CPK may refer to:*Cpk, a measure of process capability*CPK coloring, a way to color atoms when visualizing molecular models*"C.P.K." , a 1995 song by Unwritten Law from their album Blue Room*Cabbage Patch Kids*California Pizza Kitchen...
, model of the DNA double-helix. Animated molecular models, such as the wire, or skeletal, type shown at the top of this article, allow one to visually explore the three-dimensional (3D) structure of DNA. Another type of DNA model is the space-filling, or CPK
CPK
CPK may refer to:*Cpk, a measure of process capability*CPK coloring, a way to color atoms when visualizing molecular models*"C.P.K." , a 1995 song by Unwritten Law from their album Blue Room*Cabbage Patch Kids*California Pizza Kitchen...
, model.
The hydrogen bonding dynamics and proton exchange is very different by many orders of magnitude between the two systems of fully hydrated DNA and water molecules in ice. Thus, the DNA dynamics is complex, involving nanosecond and several tens of picosecond time scales, whereas that of liquid ice is on the picosecond time scale, and that of proton exchange in ice is on the millisecond time scale. The proton exchange rates in DNA and attached proteins may vary from picosecond to nanosecond, minutes or years, depending on the exact locations of the exchanged protons in the large biopolymers.
A simple harmonic oscillator
Harmonic oscillator
In classical mechanics, a harmonic oscillator is a system that, when displaced from its equilibrium position, experiences a restoring force, F, proportional to the displacement, x: \vec F = -k \vec x \, where k is a positive constant....
'vibration' is only an oversimplified dynamic representation of the longitudinal vibrations of the DNA intertwined helices which were found to be anharmonic
Anharmonicity
In classical mechanics, anharmonicity is the deviation of a system from being a harmonic oscillator. An oscillator that is not oscillating in simple harmonic motion is known as an anharmonic oscillator where the system can be approximated to a harmonic oscillator and the anharmonicity can be...
rather than harmonic as often assumed in quantum dynamic simulations
Molecular dynamics
Molecular dynamics is a computer simulation of physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a period of time, giving a view of the motion of the atoms...
of DNA.
DNA structure
The structure of DNADNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
shows a variety of forms, both double-stranded and single-stranded. The mechanical properties of DNA, which are directly related to its structure, are a significant problem for cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
. Every process which binds or reads DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
is able to use or modify the mechanical properties of DNA for purposes of recognition, packaging and modification. The extreme length (a chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
may contain a 10 cm long DNA strand), relative rigidity and helical structure of DNA has led to the evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
of histone
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
s and of enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s such as topoisomerase
Topoisomerase
Topoisomerases are enzymes that regulate the overwinding or underwinding of DNA. The winding problem of DNA arises due to the intertwined nature of its double helical structure. For example, during DNA replication, DNA becomes overwound ahead of a replication fork...
s and helicase
Helicase
Helicases are a class of enzymes vital to all living organisms. They are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two annealed nucleic acid strands using energy derived from ATP hydrolysis.-Function:Many cellular processes Helicases are a...
s to manage a cell's DNA. The properties of DNA are closely related to its molecular structure and sequence, particularly the weakness of the hydrogen bonds and electronic interactions that hold strands of DNA together compared to the strength of the bonds within each strand.
Experimental techniques which can directly measure the mechanical properties of DNA are relatively new, and high-resolution visualization in solution is often difficult. Nevertheless, scientists have uncovered large amount of data on the mechanical properties of this polymer, and the implications of DNA's mechanical properties on cellular processes is a topic of active current research.
The DNA found in many cells can be macroscopic in length - a few centimetres long for each human chromosome. Consequently, cells must compact or "package" DNA to carry it within them. In eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s this is carried by spool-like protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s known as histone
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
s, around which DNA winds. It is the further compaction of this DNA-protein complex which produces the well known mitotic eukaryotic chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s.
Alternate non-double-helical models have been proposed for the in vivo structure of DNA, such as in plasmid
Plasmid
In microbiology and genetics, a plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA. They are double-stranded and, in many cases, circular...
s and chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
. Such "side-by-side" models of DNA were proposed early in the history of molecular biology
History of molecular biology
The history of molecular biology begins in the 1930s with the convergence of various, previously distinct biological disciplines: biochemistry, genetics, microbiology, and virology...
, but these were set aside in favor of the double-helical model due to X-ray crystallography
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
of DNA duplexes and later the nucleosome core particle, as well as the discovery of topoisomerases, and these non-double-helical models are not currently accepted by the mainstream scientific community.
DNA structure determination using molecular modeling and DNA X-ray patterns
After DNA has been separated and purified by standard biochemical techniques one has a sample in a jar much like in the figure at the top of this article. Below are the main steps involved in generating structural information from X-ray diffraction studies of oriented DNA fibers that are drawn from the hydrated DNA sample with the help of molecular models of DNA that are combined with crystallographic and mathematical analysis of the X-ray patterns.
Paracrystalline lattice models of B-DNA structures
Paracrystalline
Paracrystalline materials are defined as having short and medium range ordering in their lattice but lacking long-range ordering at least in one direction....
, or paracrystal, is a molecular or atomic lattice with significant amounts (e.g., larger than a few percent) of partial disordering of molecular arrangements. Limiting cases of the paracrystal model are nanostructure
Nanostructure
A nanostructure is an object of intermediate size between molecular and microscopic structures.In describing nanostructures it is necessary to differentiate between the number of dimensions on the nanoscale. Nanotextured surfaces have one dimension on the nanoscale, i.e., only the thickness of the...
s, such as glass
Glass
Glass is an amorphous solid material. Glasses are typically brittle and optically transparent.The most familiar type of glass, used for centuries in windows and drinking vessels, is soda-lime glass, composed of about 75% silica plus Na2O, CaO, and several minor additives...
es, liquid
Liquid
Liquid is one of the three classical states of matter . Like a gas, a liquid is able to flow and take the shape of a container. Some liquids resist compression, while others can be compressed. Unlike a gas, a liquid does not disperse to fill every space of a container, and maintains a fairly...
s, etc., that may possess only local ordering and no global order. A simple example of a paracrystalline lattice is shown in the following figure for a silica glass:
Liquid crystal
Liquid crystal
Liquid crystals are a state of matter that have properties between those of a conventional liquid and those of a solid crystal. For instance, an LC may flow like a liquid, but its molecules may be oriented in a crystal-like way. There are many different types of LC phases, which can be...
s also have paracrystalline rather than crystal
Crystal
A crystal or crystalline solid is a solid material whose constituent atoms, molecules, or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions. The scientific study of crystals and crystal formation is known as crystallography...
line structures.
Highly hydrated B-DNA occurs naturally in living cells in such a paracrystalline state, which is a dynamic one in spite of the relatively rigid DNA double-helix stabilized by parallel hydrogen bonds between the nucleotide base-pairs in the two complementary, helical DNA chains (see figures). For simplicity most DNA molecular models omit both water and ions dynamically bound to B-DNA, and are thus less useful for understanding the dynamic behaviors of B-DNA in vivo. The physical and mathematical analysis of X-ray and spectroscopic data for paracrystalline B-DNA is therefore much more complicated than that of crystalline, A-DNA X-ray diffraction patterns. The paracrystal model is also important for DNA technological applications such as DNA nanotechnology
DNA nanotechnology
DNA nanotechnology is a branch of nanotechnology which uses the molecular recognition properties of DNA and other nucleic acids to create designed, artificial structures out of DNA for technological purposes. In this field, DNA is used as a structural material rather than as a carrier of genetic...
. Novel techniques that combine X-ray diffraction of DNA with X-ray microscopy in hydrated living cells are now also being developed.
Genomic and biotechnology applications of DNA molecular modeling
DNA nanotechnology
DNA nanotechnology is a branch of nanotechnology which uses the molecular recognition properties of DNA and other nucleic acids to create designed, artificial structures out of DNA for technological purposes. In this field, DNA is used as a structural material rather than as a carrier of genetic...
. Two-dimensional DNA junction arrays have been visualized by Atomic force microscopy.
DNA molecular modeling has various uses in genomics
Genomics
Genomics is a discipline in genetics concerning the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis,...
and biotechnology
Biotechnology
Biotechnology is a field of applied biology that involves the use of living organisms and bioprocesses in engineering, technology, medicine and other fields requiring bioproducts. Biotechnology also utilizes these products for manufacturing purpose...
, with research applications ranging from DNA repair to PCR and DNA nanostructures. These include computer molecular models of molecules as varied as RNA polymerase, an E. coli, bacterial DNA primase template suggesting very complex dynamics at the interfaces between the enzymes and the DNA template, and molecular models of the mutagenic, chemical interaction of potent carcinogen molecules with DNA. These are all represented in the gallery below.
Technological application include a DNA biochip and DNA nanostructures designed for DNA computing
DNA computing
DNA computing is a form of computing which uses DNA, biochemistry and molecular biology, instead of the traditional silicon-based computer technologies. DNA computing, or, more generally, biomolecular computing, is a fast developing interdisciplinary area...
and other dynamic applications of DNA nanotechnology
DNA nanotechnology
DNA nanotechnology is a branch of nanotechnology which uses the molecular recognition properties of DNA and other nucleic acids to create designed, artificial structures out of DNA for technological purposes. In this field, DNA is used as a structural material rather than as a carrier of genetic...
.
The image at right is of self-assembled DNA nanostructures. The DNA “tile” structure in this image consists of four branched junctions oriented at 90° angles. Each tile consists of nine DNA oligonucleotides as shown; such tiles serve as the primary “building block” for the assembly of the DNA nanogrids shown in the AFM micrograph.
Quadruplex DNA may be involved in certain cancers. Images of quadruplex DNA are in the gallery below.
See also
Further reading
- Applications of Novel Techniques to Health Foods, Medical and Agricultural Biotechnology.(June 2004) I. C. Baianu, P. R. Lozano, V. I. Prisecaru and H. C. Lin., q-bio/0406047.
- F. Bessel, Untersuchung des Theils der planetarischen Störungen, Berlin Abhandlungen (1824), article 14.
- Sir Lawrence Bragg, FRS. The Crystalline State, A General survey. London: G. Bells and Sons, Ltd., vols. 1 and 2., 1966., 2024 pages.
- Cantor, C. R. and Schimmel, P.R. Biophysical Chemistry, Parts I and II., San Franscisco: W.H. Freeman and Co. 1980. 1,800 pages.
- Voet, D. and J.G. Voet. Biochemistry, 2nd Edn., New York, Toronto, Singapore: John Wiley & Sons, Inc., 1995, ISBN 0-471-58651-X., 1361 pages.
- Watson, G. N. A Treatise on the Theory of Bessel Functions., (1995) Cambridge University Press. ISBN 0-521-48391-3.
- Watson, James D. Molecular Biology of the Gene. New York and Amsterdam: W.A. Benjamin, Inc. 1965., 494 pages.
- Wentworth, W.E. Physical Chemistry. A short course., Malden ( Mass.): Blackwell Science, Inc. 2000.
- Herbert R. Wilson, FRS. Diffraction of X-rays by proteins, Nucleic Acids and Viruses., London: Edward Arnold (Publishers) Ltd. 1966.
- Kurt Wuthrich. NMR of Proteins and Nucleic Acids., New York, Brisbane,Chicester, Toronto, Singapore: J. Wiley & Sons. 1986., 292 pages.
- Zhang CT, Zhang R, Ou HY (2003). "The Z curve database: a graphic representation of genome sequences". Bioinformatics 19 (5): 593-599. PMID 12651717
External links
- DNA the Double Helix Game From the official Nobel Prize web site
- MDDNA: Structural Bioinformatics of DNA
- Double Helix 1953–2003 National Centre for Biotechnology Education
- DNAlive: a web interface to compute DNA physical properties. Also allows cross-linking of the results with the UCSC Genome browserGenome browserA genome browser is a graphical interface for display of information from a biological database for genomic data. Genome browsers enable researchers to visualize and browse entire genomes with annotated data including gene prediction and structure, proteins, expression, regulation, variation,...
and DNA dynamics. - Further details of mathematical and molecular analysis of DNA structure based on X-ray data
- Bessel functions corresponding to Fourier transforms of atomic or molecular helices.
- overview of STM/AFM/SNOM principles with educative videos
Databases for DNA molecular models and sequences
X-ray diffraction- NDB ID: UD0017 Database
- X-ray Atlas -database
- PDB files of coordinates for nucleic acid structures from X-ray diffraction by NA (incl. DNA) crystals
- Structure factors dowloadable files in CIF format
Neutron scattering
- ISIS neutron sourceISIS neutron sourceISIS is a pulsed neutron and muon source. It is situated at the Rutherford Appleton Laboratory on the Harwell Science and Innovation Campus in Oxfordshire, United Kingdom and is part of the Science and Technology Facilities Council...
: ISIS pulsed neutron source:A world centre for science with neutrons & muons at Harwell, near Oxford, UK.
X-ray microscopy
Electron microscopy
NMR databases
- NMR Atlas--database
- mmcif downloadable coordinate files of nucleic acids in solution from 2D-FT NMR data
- NMR constraints files for NAs in PDB format
Genomic and structural databases
- CBS Genome Atlas Database — contains examples of base skews.
- The Z curve database of genomes — a 3-dimensional visualization and analysis tool of genomes.
- DNA and other nucleic acids' molecular models: Coordinate files of nucleic acids molecular structure models in PDB and CIF formats
Atomic force microscopy