DNA sequencing and genomics

One of the most fundamental technologies developed to study genetics, DNA sequencing allows researchers to determine the sequence of nucleotides in DNA fragments. Developed in 1977 by Frederick Sanger and coworkers, chain-termination sequencing is now routinely used to sequence DNA fragments. With this technology, researchers have been able to study the molecular sequences associated with many human diseases. As sequencing has become less expensive, researchers have sequenced the genomes of many organisms, using computational tools to stitch together the sequences of many different fragments (a process called genome assembly). These technologies were used to sequence the human genome, leading to the completion of the Human Genome Project in 2003. New high-throughput sequencing technologies are dramatically lowering the cost of DNA sequencing, with many researchers hoping to bring the cost of resequencing a human genome down to a thousand dollars. The large amount of sequence data available has created the field of genomics, research that uses computational tools to search for and analyze patterns in the full genomes of organisms. Genomics can also be considered a subfield of bioinformatics, which uses computational approaches to analyze large sets of biological data.

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Molecular models of DNA

Molecular models of DNA structures are representations of the molecular geometry and topology of Deoxyribonucleic acid (DNA) molecules using one of several means, such as: closely packed spheres (CPK models) made of plastic, metal wires for 'skeletal models', graphic computations and animations by computers, artistic rendering, and so on, with the aim of simplifying and presenting the essential, physical and chemical, properties of DNA molecular structures either in vivo or in vitro. Computer molecular models also allow animations and molecular dynamics simulations that are very important for understanding how DNA functions in vivo. Thus, 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 nucleotide 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 geometries can also be computed, at least in principle, by employing ab initio quantum chemistry methods that have high accuracy for small molecules. Such quantum geometries define an important class of ab initio molecular models of DNA whose exploration has barely started.

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