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Kinetic Proofreading
Kinetic proofreading (or kinetic amplification) is a mechanism for error correction in biochemical reactions, proposed independently by John Hopfield (1974) and Jacques Ninio (1975). Kinetic proofreading allows enzymes to discriminate between two possible reaction pathways leading to correct or incorrect products with an accuracy higher than what one would predict based on the difference in the activation energy between these two pathways. Increased specificity is obtained by introducing an irreversible step exiting the pathway, with reaction intermediates leading to incorrect products more likely to prematurely exit the pathway than reaction intermediates leading to the correct product. If the exit step is fast relative to the next step in the pathway, the specificity can be increased by a factor of up to the ratio between the two exit rate constants. (If the next step is fast relative to the exit step, specificity will not be increased because there will not be enough time for ...
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Enzyme Catalysis
Enzyme catalysis is the increase in the rate of a process by an "enzyme", a biological molecule. Most enzymes are proteins, and most such processes are chemical reactions. Within the enzyme, generally catalysis occurs at a localized site, called the active site. Most enzymes are made predominantly of proteins, either a single protein chain or many such chains in a multi-subunit complex. Enzymes often also incorporate non-protein components, such as metal ions or specialized organic molecules known as cofactor (e.g. adenosine triphosphate). Many cofactors are vitamins, and their role as vitamins is directly linked to their use in the catalysis of biological process within metabolism. Catalysis of biochemical reactions in the cell is vital since many but not all metabolically essential reactions have very low rates when uncatalysed. One driver of protein evolution is the optimization of such catalytic activities, although only the most crucial enzymes operate near catalytic ...
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Conformational Proofreading
Conformational proofreading or conformational selection is a general mechanism of molecular recognition systems, suggested by Yonatan Savir and Tsvi Tlusty, in which introducing an energetic barrier - such as a structural mismatch between a molecular recognizer and its target - enhances the recognition specificity and quality. Conformational proofreading does not require the consumption of energy and may therefore be used in any molecular recognition system. Conformational proofreading is especially useful in scenarios where the recognizer has to select the appropriate target among many similar competitors. Proteins evolve the capacity for conformational proofreading through fine-tuning their geometry, flexibility and chemical interactions with the target. Balancing correct and incorrect binding Molecular recognition takes place in a noisy, crowded biological environment and the recognizer often has to cope with the task of selecting its target among a variety of similar comp ...
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Biological Processes
Biological processes are those processes that are necessary for an organism to live and that shape its capacities for interacting with its environment. Biological processes are made of many chemical reactions or other events that are involved in the persistence and transformation of life forms. Regulation of biological processes occurs when any process is modulated in its frequency, rate or extent. Biological processes are regulated by many means; examples include the control of gene expression, protein modification or interaction with a protein or substrate molecule. * Homeostasis: regulation of the internal environment to maintain a constant state; for example, sweating to reduce temperature * Organization: being structurally composed of one or more cells – the basic units of life * Metabolism: transformation of energy by converting chemicals and energy into cellular components (anabolism) and decomposing organic matter ( catabolism). Living things require energy to mai ...
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Universal First Passage Time
Universal is the adjective for universe. Universal may also refer to: Companies * NBCUniversal, a media and entertainment company that is a subsidiary of Comcast ** Universal Animation Studios, an American Animation studio, and a subsidiary of NBCUniversal ** Universal TV, a television channel owned by NBCUniversal ** Universal Kids, an American current television channel, formerly known as Sprout, owned by NBCUniversal ** Universal Pictures, an American film studio, and a subsidiary of NBCUniversal ** Universal Television, a television division owned by NBCUniversal Content Studios ** Universal Destinations & Experiences, the theme park unit of NBCUniversal * Universal Airlines (other) * Universal Avionics, a manufacturer of flight control components * Universal Corporation, an American tobacco company * Universal Display Corporation, a manufacturer of displays * Universal Edition, a classical music publishing firm, founded in Vienna in 1901 * Universal Entertainment, a ...
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Markov Process
In probability theory and statistics, a Markov chain or Markov process is a stochastic process describing a sequence of possible events in which the probability of each event depends only on the state attained in the previous event. Informally, this may be thought of as, "What happens next depends only on the state of affairs ''now''." A countably infinite sequence, in which the chain moves state at discrete time steps, gives a discrete-time Markov chain (DTMC). A continuous-time process is called a continuous-time Markov chain (CTMC). Markov processes are named in honor of the Russian mathematician Andrey Markov. Markov chains have many applications as statistical models of real-world processes. They provide the basis for general stochastic simulation methods known as Markov chain Monte Carlo, which are used for simulating sampling from complex probability distributions, and have found application in areas including Bayesian statistics, biology, chemistry, economics, finance, i ...
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First Passage Time
In statistics, first-hitting-time models are simplified models that estimate the amount of time that passes before some random or stochastic process crosses a barrier, boundary or reaches a specified state, termed the first hitting time, or the first passage time. Accurate models give insight into the physical system under observation, and have been the topic of research in very diverse fields, from economics to ecology. The idea that a first hitting time of a stochastic process might describe the time to occurrence of an event has a long history, starting with an interest in the first passage time of Wiener diffusion processes in economics and then in physics in the early 1900s. Modeling the probability of financial ruin as a first passage time was an early application in the field of insurance. An interest in the mathematical properties of first-hitting-times and statistical models and methods for analysis of survival data appeared steadily between the middle and end of the 20t ...
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Major Histocompatibility Complex
The major histocompatibility complex (MHC) is a large Locus (genetics), locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for Cell (biology), cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules. Its name comes from its discovery during the study of transplanted tissue compatibility. Later studies revealed that tissue rejection due to incompatibility is only a facet of the full function of MHC molecules, which is to bind an antigen derived from self-proteins, or from pathogens, and bring the antigen presentation to the cell surface for recognition by the appropriate T cell, T-cells. MHC molecules mediate the interactions of leukocytes, also called white blood cells (WBCs), with other leukocytes or with body cells. The MHC determines donor compatibility for organ transplant, as well as one's susceptibility to autoimmune diseases. In a cell, protein molecules of the host's own pheno ...
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Antigen
In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. Antigens can be proteins, peptides (amino acid chains), polysaccharides (chains of simple sugars), lipids, or nucleic acids. Antigens exist on normal cells, cancer cells, parasites, viruses, fungus, fungi, and bacteria. Antigens are recognized by antigen receptors, including antibodies and T-cell receptors. Diverse antigen receptors are made by cells of the immune system so that each cell has a specificity for a single antigen. Upon exposure to an antigen, only the lymphocytes that recognize that antigen are activated and expanded, a process known as clonal selection. In most cases, antibodies are ''antigen-specific'', meaning that an antibody can only react to and bind one specific antigen; in some instances, however, antibodies may cr ...
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T Cell Receptor
The T-cell receptor (TCR) is a protein complex, located on the surface of T cells (also called T lymphocytes). They are responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen peptides is of relatively low affinity and is biologically degenerate (that is, many TCRs recognize the same antigen peptide, and many antigen peptides are recognized by the same TCR). The TCR is composed of two different protein chains (that is, it is a hetero dimer). In humans, in 95% of T cells the TCR consists of an alpha (α) chain and a beta (β) chain (encoded by ''TRA'' and ''TRB'', respectively), whereas in 5% of T cells the TCR consists of gamma and delta (γ/δ) chains (encoded by '' TRG'' and '' TRD'', respectively). This ratio changes during ontogeny and in diseased states (such as leukemia). It also differs between species. Orthologues of the 4 loci have been mapped in various species. ...
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DNA Repair
DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified in Cell (biology), cells, by internal metabolism, metabolic by-products, and by external ionizing radiation, ultraviolet light, and medicines, resulting in spontaneous DNA damage involving tens of thousands of individual molecular lesions per cell per day. DNA modifications can also be programmed. Molecular lesions can cause structural damage to the DNA molecule, and can alter or eliminate the cell's ability for Transcription (biology), transcription and gene expression. Other lesions may induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells following mitosis. Consequently, DNA repair as part of the DNA damage response (DDR) is constantly active. When normal repair proce ...
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Homologous Recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organisms but may be also RNA in viruses). Homologous recombination is widely used by cells to accurately DNA repair, repair harmful DNA breaks that occur on both strands of DNA, known as double-strand breaks (DSB), in a process called homologous recombinational repair (HRR). Homologous recombination also produces new combinations of DNA sequences during meiosis, the process by which eukaryotes make gamete cells, like sperm and ovum, egg cells in animals. These new combinations of DNA represent genetic variation in offspring, which in turn enables populations to Adaptation, adapt during the course of evolution. Homologous recombination is also used in horizontal gene transfer to exchange genetic material between different strains and species ...
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Aminoacyl TRNA Synthetase
An aminoacyl-tRNA synthetase (aaRS or ARS), also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its corresponding tRNA. It does so by catalyzing the transesterification of a specific cognate amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA. In humans, the 20 different types of aa-tRNA are made by the 20 different aminoacyl-tRNA synthetases, one for each amino acid of the genetic code. This is sometimes called "charging" or "loading" the tRNA with an amino acid. Once the tRNA is charged, a ribosome can transfer the amino acid from the tRNA onto a growing peptide, according to the genetic code. Aminoacyl tRNA therefore plays an important role in RNA Translation (biology), translation, the expression of genes to create proteins. Mechanism The synthetase first binds Adenosine triphosphate, ATP and the corresponding amino acid (or its Amino acid synthesis, precursor) to form an aminoacyl-adenylate, relea ...
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