Phi Value Analysis
Phi value analysis, \varphi analysis, or \varphi-value analysis is an experimental protein engineering technique for studying structures of the transition state and intermediates in protein folding and conformational changes. The structure of the folding transition state has to be found from kinetic measurements and is not accessible by equilibrium methods such as protein NMR or X-ray crystallography and intermediates are often mobile and partly unstructured by definition. In \varphi -value analysis, the folding kinetics and conformational folding stability of the wild-type protein are compared with those of point mutants to find ''phi values''. These measure the mutant residue's energetic contribution to the folding transition state, which reveals the degree of native structure around the mutated residue in the transition state, by accounting for the relative free energies of the unfolded state, the folded state, and the transition state for the wild-type and mutant proteins ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Protein Engineering
Protein engineering is the process of developing useful or valuable proteins through the design and production of unnatural polypeptides, often by altering amino acid sequences found in nature. It is a young discipline, with much research taking place into the understanding of protein folding and recognition for protein design principles. It has been used to improve the function of many enzymes for industrial catalysis. It is also a product and services market, with an estimated value of $168 billion by 2017. There are two general strategies for protein engineering: rational protein design and directed evolution. These methods are not mutually exclusive; researchers will often apply both. In the future, more detailed knowledge of protein structure and function, and advances in high-throughput screening, may greatly expand the abilities of protein engineering. Eventually, even unnatural amino acids may be included, via newer methods, such as expanded genetic code, that allow e ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Chymotrypsin
Chymotrypsin (, chymotrypsins A and B, alpha-chymar ophth, avazyme, chymar, chymotest, enzeon, quimar, quimotrase, alpha-chymar, alpha-chymotrypsin A, alpha-chymotrypsin) is a digestive enzyme component of pancreatic juice acting in the duodenum, where it performs proteolysis, the breakdown of proteins and polypeptides. Chymotrypsin preferentially cleaves peptide amide bonds where the side chain of the amino acid N-terminal to the scissile amide bond (the P1 position) is a large hydrophobic amino acid ( tyrosine, tryptophan, and phenylalanine). These amino acids contain an aromatic ring in their side chain that fits into a hydrophobic pocket (the S1 position) of the enzyme. It is activated in the presence of trypsin. The hydrophobic and shape complementarity between the peptide substrate P1 side chain and the enzyme S1 binding cavity accounts for the substrate specificity of this enzyme. Chymotrypsin also hydrolyzes other amide bonds in peptides at slower rates, particularly th ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an Amine, α-amino group (which is in the protonated –NH3+ form under Physiological condition, biological conditions), a carboxylic acid group (which is in the deprotonated –COO− form under biological conditions), and an imidazole side chain (which is partially protonated), classifying it as a positively charged amino acid at physiological pH. Initially thought essential amino acid, essential only for infants, it has now been shown in longer-term studies to be essential for adults also. It is Genetic code, encoded by the Genetic code, codons CAU and CAC. Histidine was first isolated by Albrecht Kossel and Sven Gustaf Hedin in 1896. The name stems from its discovery in tissue, from ''histós'' "tissue". It is also a Precursor (chemistry), precursor to histamine, a vital inflammatory agent in immune responses. The acyl radical (chemistry), radical is histidyl. Pro ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Molecular Dynamics
Molecular dynamics (MD) is a computer simulation method for analyzing the Motion (physics), physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamics (mechanics), dynamic "evolution" of the system. In the most common version, the trajectory, trajectories of atoms and molecules are determined by Numerical integration, numerically solving Newton's laws of motion, Newton's equations of motion for a system of interacting particles, where Force (physics), forces between the particles and their potential energy, potential energies are often calculated using interatomic potentials or molecular mechanics, molecular mechanical Force field (chemistry), force fields. The method is applied mostly in chemical physics, materials science, and biophysics. Because molecular systems typically consist of a vast number of particles, it is impossible to determine the properties of such complex systems analyt ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Bacteria
Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the first life forms to appear on Earth, and are present in most of its habitats. Bacteria inhabit the air, soil, water, Hot spring, acidic hot springs, radioactive waste, and the deep biosphere of Earth's crust. Bacteria play a vital role in many stages of the nutrient cycle by recycling nutrients and the nitrogen fixation, fixation of nitrogen from the Earth's atmosphere, atmosphere. The nutrient cycle includes the decomposition of cadaver, dead bodies; bacteria are responsible for the putrefaction stage in this process. In the biological communities surrounding hydrothermal vents and cold seeps, extremophile bacteria provide the nutrients needed to sustain life by converting dissolved compounds, suc ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Alan Fersht
Sir Alan Roy Fersht (born 21 April 1943) is a British chemist at the MRC Laboratory of Molecular Biology, Cambridge, and an Emeritus Professor in the Department of Chemistry at the University of Cambridge. He was Master of Gonville and Caius College, Cambridge from 2012 to 2018. He works at the interface of chemistry, molecular biology and biophysics on protein science, and is sometimes described as a founder of protein engineering. Early life and education Fersht was born on 21 April 1943 in Hackney, London. His father, Philip, was a ladies' tailor and his mother, Betty, a dressmaker. His grandparents were Jewish immigrants from Poland, Lithuania and Belarus. He was educated at Sir George Monoux Grammar School, an all-boys grammar school in Walthamstow, London. He was a keen chess player and was the Essex County Junior champion in 1961. He was awarded a State Scholarship to read Natural Sciences at Gonville and Caius College, Cambridge, where he obtained First Class in P ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Energy Landscape
Energy () is the quantitative property that is transferred to a body or to a physical system, recognizable in the performance of work and in the form of heat and light. Energy is a conserved quantity—the law of conservation of energy states that energy can be converted in form, but not created or destroyed. The unit of measurement for energy in the International System of Units (SI) is the joule (J). Forms of energy include the kinetic energy of a moving object, the potential energy stored by an object (for instance due to its position in a field), the elastic energy stored in a solid object, chemical energy associated with chemical reactions, the radiant energy carried by electromagnetic radiation, the internal energy contained within a thermodynamic system, and rest energy associated with an object's rest mass. These are not mutually exclusive. All living organisms constantly take in and release energy. The Earth's climate and ecosystems processes are driven pri ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Hammond's Postulate
Hammond's postulate (or alternatively the Hammond–Leffler postulate), is a hypothesis in physical organic chemistry which describes the geometric structure of the transition state in an organic chemical reaction. First proposed by George Hammond in 1955, the postulate states that: If two states, as, for example, a transition state and an unstable intermediate, occur consecutively during a reaction process and have nearly the same energy content, their interconversion will involve only a small reorganization of the molecular structures. Therefore, the geometric structure of a state can be predicted by comparing its energy to the species neighboring it along the reaction coordinate. For example, in an ''exothermic'' reaction the transition state is closer in energy to the reactants than to the products. Therefore, the transition state will be more geometrically similar to the reactants than to the products. In contrast, however, in an ''endothermic'' reaction the transition s ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Statistical Mechanics
In physics, statistical mechanics is a mathematical framework that applies statistical methods and probability theory to large assemblies of microscopic entities. Sometimes called statistical physics or statistical thermodynamics, its applications include many problems in a wide variety of fields such as biology, neuroscience, computer science Computer science is the study of computation, information, and automation. Computer science spans Theoretical computer science, theoretical disciplines (such as algorithms, theory of computation, and information theory) to Applied science, ..., information theory and sociology. Its main purpose is to clarify the properties of matter in aggregate, in terms of physical laws governing atomic motion. Statistical mechanics arose out of the development of classical thermodynamics, a field for which it was successful in explaining macroscopic physical properties—such as temperature, pressure, and heat capacity—in terms of microscop ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Valerie Daggett
Valerie Daggett is a professor of bioengineering at the University of Washington in Seattle, Washington, United States. Education and career Daggett has a B.S. from Reed College. She received her Ph.D. from the University of California, San Francisco, advised by Irwin Kuntz and Peter Kollman, and subsequently held a postdoctoral position at Stanford University with Michael Levitt, a co-recipient of the 2013 Nobel Prize in Chemistry. As of 2021, she is also the chief executive officer of AltPep, a biomedical startup that was a spinoff from her research at the University of Washington. Research Her laboratory focuses on work in molecular dynamics simulations of proteins and other biomolecules. Daggett is well known for large-scale simulations of protein folding, especially unfolding, and native state dynamics through her "dynameomics" project. In 2005, the Daggett laboratory was awarded a supercomputing grant by the U.S. Department of Energy, which was renewed for almo ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Phi Value Illustration
Phi ( ; uppercase Φ, lowercase φ or ϕ; ''pheî'' ; Modern Greek: ''fi'' ) is the twenty-first letter of the Greek alphabet. In Archaic and Classical Greek (c. 9th to 4th century BC), it represented an aspirated voiceless bilabial plosive (), which was the origin of its usual romanization as . During the later part of Classical Antiquity, in Koine Greek (c. 4th century BC to 4th century AD), its pronunciation shifted to a voiceless bilabial fricative (), and by the Byzantine Greek period (c. 4th century AD to 15th century AD) it developed its modern pronunciation as a voiceless labiodental fricative (). The romanization of the Modern Greek phoneme is therefore usually . It may be that phi originated as the letter qoppa (Ϙ, ϙ), and initially represented the sound before shifting to Classical Greek . In traditional Greek numerals, phi has a value of 500 () or 500,000 (). The Cyrillic letter Ef (Ф, ф) descends from phi. Like other Greek letters, lowercase phi (enco ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Barnase
Barnase (a portmanteau of "BActerial" "RiboNucleASE") is a bacterial protein that consists of 110 amino acids and has ribonuclease activity. It is synthesized and secreted by the bacterium '' Bacillus amyloliquefaciens'', but is lethal to the cell when expressed without its inhibitor barstar. The inhibitor binds to and occludes the ribonuclease active site, preventing barnase from damaging the cell's RNA after it has been synthesized but before it has been secreted. The barnase/barstar complex is noted for its extraordinarily tight protein-protein binding, with an on-rate of 108s−1M−1. Protein folding studies Barnase has no disulfide bonds, nor does it require divalent cations or non-peptide components to fold. This simplicity, in combination with its reversible folding transition, means that barnase has been extensively studied in order to understand how proteins fold. The folding of barnase has been extensively studied in the laboratory of Alan Fersht, who used it as t ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |