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Phi Value Analysis
Phi value analysis, \phi analysis, or \phi-value analysis is an experimental protein engineering technique for studying the structure of the folding transition state of small protein domains that fold in a two-state manner. The structure of the folding transition state is hard to find using methods such as protein NMR or X-ray crystallography because folding transitions states are mobile and partly unstructured by definition. In \phi -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. The protein's residues are mutated one by one to ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Engineering
Protein engineering is the process of developing useful or valuable proteins. 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 encoding novel amino acids in genetic code. Approaches Rational design In rational protein design, a scientist uses ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form under biological conditions), and a side chain consisting of a hydroxymethyl group, classifying it as a polar amino acid. It can be synthesized in the human body under normal physiological circumstances, making it a nonessential amino acid. It is encoded by the codons UCU, UCC, UCA, UCG, AGU and AGC. Occurrence This compound is one of the naturally occurring proteinogenic amino acids. Only the L-stereoisomer appears naturally in proteins. It is not essential to the human diet, since it is synthesized in the body from other metabolites, including glycine. Serine was first obtained from silk protein, a particularly rich source, in 1865 by Emil Cramer. Its name is derived from the Latin for silk, ''sericum''. Serine's structure was estab ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Molecular Dynamics
Molecular dynamics (MD) is a computer simulation method for analyzing the 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 dynamic "evolution" of the system. In the most common version, the trajectories of atoms and molecules are determined by numerically solving Newton's equations of motion for a system of interacting particles, where forces between the particles and their potential energies are often calculated using interatomic potentials or molecular mechanical 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 analytically; MD simulation circumvents this problem by using numerical methods. However, long MD simulations are mathematically ill-conditioned, generating cumulative errors in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of 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 soil, water, acidic hot springs, radioactive waste, and the deep biosphere of Earth's crust. Bacteria are vital in many stages of the nutrient cycle by recycling nutrients such as the fixation of nitrogen from the atmosphere. The nutrient cycle includes the decomposition of 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, such as hydrogen sulphide and methane, to energy. Bacteria also live in symbiotic and parasitic relationsh ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 on protein folding, 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, Romania, 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 Pt I of the Natural Sciences Tripos in 1964, First Class i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Energy Landscape
An energy landscape is a mapping of possible states of a system. The concept is frequently used in physics, chemistry, and biochemistry, e.g. to describe all possible conformations of a molecular entity, or the spatial positions of interacting molecules in a system, or parameters and their corresponding energy levels, typically Gibbs free energy. Geometrically, the energy landscape is the graph of the energy function across the configuration space of the system. The term is also used more generally in geometric perspectives to mathematical optimization, when the domain of the loss function is the parameter space of some system. Applications The term is useful when examining protein folding; while a protein can theoretically exist in a nearly infinite number of conformations along its energy landscape, in reality proteins fold (or "relax") into secondary and tertiary structures that possess the lowest possible free energy. The key concept in the energy landscape approach to pro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 st ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Statistical Mechanics
In physics, statistical mechanics is a mathematical framework that applies statistical methods and probability theory to large assemblies of microscopic entities. It does not assume or postulate any natural laws, but explains the macroscopic behavior of nature from the behavior of such ensembles. 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 microscopic parameters that fluctuate about average values and are characterized by probability distributions. This established the fields of statistical thermodynamics and statistical physics. The founding of the field of statistical mechanics is generally credited to three physicists: *Ludwig Boltzmann, who developed the fundamental interpretation of entropy in terms of a collection of microstates *James Clerk Maxwell, who developed models of probability distr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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] |
Phi Value Illustration
Phi (; uppercase Φ, lowercase φ or ϕ; grc, ϕεῖ ''pheî'' ; Modern Greek: ''fi'' ) is the 21st letter of the Greek alphabet. In Archaic and Classical Greek (c. 9th century BC 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 that of 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. As with other Greek ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 the te ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Four genes in the human genome code for ubiquitin: UBB, UBC, UBA52 and RPS27A. The addition of ubiquitin to a substrate protein is called ubiquitylation (or, alternatively, ubiquitination or ubiquitinylation). Ubiquitylation affects proteins in many ways: it can mark them for degradation via the proteasome, alter their cellular location, affect their activity, and promote or prevent protein interactions. Ubiquitylation involves three main steps: activation, conjugation, and ligation, performed by ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s), respectively. The result of this sequential cascade is to bind ubiquitin to lysine residues on the protein substrate via an isopeptide bond, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
