In the field of molecular modeling, docking is a method which predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex. Knowledge of the preferred orientation in turn may be used to predict the strength of association or binding affinity between two molecules using, for example, scoring functions; the associations between biologically relevant molecules such as proteins, nucleic acids and lipids play a central role in signal transduction. Furthermore, the relative orientation of the two interacting partners may affect the type of signal produced. Therefore, docking is useful for predicting both the strength and type of signal produced. Molecular docking is one of the most used methods in structure-based drug design, due to its ability to predict the binding-conformation of small molecule ligands to the appropriate target binding site. Characterisation of the binding behaviour plays an important role in rational design of drugs as well as to elucidate fundamental biochemical processes.
One can think of molecular docking as a problem of “lock-and-key”, in which one wants to find the correct relative orientation of the “key” which will open up the “lock”. Here, the protein can be thought of as the “lock” and the ligand can be thought of as a “key”. Molecular docking may be defined as an optimization problem, which would describe the “best-fit” orientation of a ligand that binds to a particular protein of interest. However, since both the ligand and the protein are flexible, a “hand-in-glove” analogy is more appropriate than “lock-and-key”. During the course of the docking process, the ligand and the protein adjust their conformation to achieve an overall "best-fit" and this kind of conformational adjustment resulting in the overall binding is referred to as "induced-fit". Molecular docking research focuses on computationally simulating the molecular recognition process, it aims to achieve an optimized conformation for both the protein and ligand and relative orientation between protein and ligand such that the free energy of the overall system is minimized.
Two approaches are popular within the molecular docking community. One approach uses a matching technique that describes the protein and the ligand as complementary surfaces; the second approach simulates the actual docking process in which the ligand-protein pairwise interaction energies are calculated. Both approaches have significant advantages as well as some limitations; these are outlined below. Geometric matching/ shape complementarity methods describe the protein and ligand as a set of features that make them dockable; these features may include molecular surface / complementary surface descriptors. In this case, the receptor’s molecular surface is described in terms of its solvent-accessible surface area and the ligand’s molecular surface is described in terms of its matching surface description; the complementarity between the two surfaces amounts to the shape matching description that may help finding the complementary pose of docking the target and the ligand molecules. Another approach is to describe the hydrophobic features of the protein using turns in the main-chain atoms.
Yet another approach is to use a Fourier shape descriptor technique. Whereas the shape complementarity based approaches are fast and robust, they cannot model the movements or dynamic changes in the ligand/ protein conformations although recent developments allow these methods to investigate ligand flexibility. Shape complementarity methods can scan through several thousand ligands in a matter of seconds and figure out whether they can bind at the protein’s active site, are scalable to protein-protein interactions, they are much more amenable to pharmacophore based approaches, since they use geometric descriptions of the ligands to find optimal binding. Simulating the docking process is much more complicated. In this approach, the protein and the ligand are separated by some physical distance, the ligand finds its position into the protein’s active site after a certain number of “moves” in its conformational space; the moves incorporate rigid body transformations such as translations and rotations, as well as internal changes to the ligand’s structure including torsion angle rotations.
Each of these moves in the conformation space of the ligand induces a total energetic cost of the system. Hence, the system's total energy is calculated after every move; the obvious advantage of docking simulation is that ligand flexibility is incorporated, whereas shape complementarity techniques must use ingenious methods to incorporate flexibility in ligands. It more models reality, whereas shape complimentary techniques are more of an abstraction. Simulation is computationally expensive, having to explore a large energy landscape. Grid-based techniques, optimization methods, increased computer speed have made docking simulation more realistic. To perform a docking screen, the first requirement is a structure of the protein of interest; the structure has been determined using a biophysical technique such as x-ray crystallography or NMR spectroscopy, but can derive from homology modeling construction. This protein structure and a database of potential ligands serve as inputs to a docking program.
The success of a docking program depends on two components: the search algorithm and the scoring function. The search space in theory consists of all possible orientations and conformations of the protein paired with the ligand. However, in practice with current computational resources, it is impossible to
An academy is an institution of secondary education, higher learning, research, or honorary membership. Academia is the worldwide group composed of professors and researchers at institutes of higher learning; the name traces back to Plato's school of philosophy, founded 385 BC at Akademia, a sanctuary of Athena, the goddess of wisdom and skill, north of Athens, Greece. The word comes from the Academy in ancient Greece, which derives from Akademos. Outside the city walls of Athens, the gymnasium was made famous by Plato as a center of learning; the sacred space, dedicated to the goddess of wisdom, had been an olive grove, hence the expression "the groves of Academe". In these gardens, the philosopher Plato conversed with followers. Plato developed his sessions into a method of teaching philosophy and in 387 BC, established what is known today as the Old Academy. By extension academia has come to mean the cultural accumulation of knowledge, its development and transmission across generations and its practitioners and transmitters.
In the 17th century, British and French scholars used the term to describe types of institutions of higher learning. Before Akademia was a school, before Cimon enclosed its precincts with a wall, it contained a sacred grove of olive trees dedicated to Athena, the goddess of wisdom, outside the city walls of ancient Athens; the archaic name for the site was Hekademia, which by classical times evolved into Akademia and was explained, at least as early as the beginning of the 6th century BC, by linking it to an Athenian hero, a legendary "Akademos". The site of Akademia was sacred to other immortals. Plato's immediate successors as "scholarch" of Akademia were Speusippus, Polemon and Arcesilaus. Scholarchs include Lacydes of Cyrene, Carneades and Philo of Larissa. Other notable members of Akademia include Aristotle, Heraclides Ponticus, Eudoxus of Cnidus, Philip of Opus and Antiochus of Ascalon. After a lapse during the early Roman occupation, Akademia was refounded as a new institution of some outstanding Platonists of late antiquity who called themselves "successors" and presented themselves as an uninterrupted tradition reaching back to Plato.
However, there cannot have been any geographical, economic or personal continuity with the original Academy in the new organizational entity. The last "Greek" philosophers of the revived Akademia in the 6th century were drawn from various parts of the Hellenistic cultural world and suggest the broad syncretism of the common culture: Five of the seven Akademia philosophers mentioned by Agathias were Syriac in their cultural origin: Hermias and Diogenes, Isidorus of Gaza, Damascius of Syria, Iamblichus of Coele-Syria and even Simplicius of Cilicia; the emperor Justinian closed the school in AD 529, a date, cited as the end of Antiquity. According to the sole witness, the historian Agathias, its remaining members looked for protection under the rule of Sassanid king Khosrau I in his capital at Ctesiphon, carrying with them precious scrolls of literature and philosophy, to a lesser degree of science. After a peace treaty between the Persian and the Byzantine empire in 532 guaranteed their personal security, some members found sanctuary in the pagan stronghold of Harran, near Edessa.
One of the last leading figures of this group was Simplicius, a pupil of Damascius, the last head of the Athenian school. It has been speculated. After his exile, may have travelled to Harran, near Edessa. From there, the students of an Academy-in-exile could have survived into the 9th century, long enough to facilitate the Arabic revival of the Neoplatonist commentary tradition in Baghdad. In ancient Greece, after the establishment of the original Academy, Plato's colleagues and pupils developed spin-offs of his method. Arcesilaus, a Greek student of Plato established the Middle Academy. Carneades, another student, established the New Academy. In 335 BC, Aristotle refined the method with his own theories and established the Lyceum in another gymnasium; the library of Alexandria in Egypt was frequented by intellectuals from Africa and Asia studying various aspects of philosophy and mathematics. The University of Timbuktu was a medieval university in Timbuktu, present-day Mali, which comprised three schools: the Mosque of Djinguereber, the Mosque of Sidi Yahya, the Mosque of Sankore.
During its zenith, the university had an average attendance of around 25,000 students within a city of around 100,000 people. In China a higher education institution Shang Xiang was founded by Shun in the Youyu era before the 21st century BC; the Imperial Central Academy at Nanjing, founded in 258, was a result of the evolution of Shang Xiang and it became the first comprehensive institution combining education and research and was divided into five faculties in 470, which became Nanjing University. In the 8th century another kind of institution of learning emerged, named Shuyuan, which were privately owned. There were thousands of Shuyuan recorded in ancient times; the degrees from them varied from one to another and those advanced Shuyuan such as Bailudong Shuyuan and Yuelu Shuyuan can be classified as higher institutions of learning. Taxila or Takshashila, in ancient India, modern-day Pakistan, was an early centre of learning, near present-day Islamabad in the city of Taxila, it is considered as one
Computational chemistry is a branch of chemistry that uses computer simulation to assist in solving chemical problems. It uses methods of theoretical chemistry, incorporated into efficient computer programs, to calculate the structures and properties of molecules and solids, it is necessary because, apart from recent results concerning the hydrogen molecular ion, the quantum many-body problem cannot be solved analytically, much less in closed form. While computational results complement the information obtained by chemical experiments, it can in some cases predict hitherto unobserved chemical phenomena, it is used in the design of new drugs and materials. Examples of such properties are structure and relative energies, electronic charge density distributions and higher multipole moments, vibrational frequencies, reactivity, or other spectroscopic quantities, cross sections for collision with other particles; the methods used cover both dynamic situations. In all cases, the computer time and other resources increase with the size of the system being studied.
That system can be a group of molecules, or a solid. Computational chemistry methods range from approximate to accurate. Ab initio methods are based on quantum mechanics and basic physical constants. Other methods are called empirical or semi-empirical because they use additional empirical parameters. Both ab initio and semi-empirical approaches involve approximations; these range from simplified forms of the first-principles equations that are easier or faster to solve, to approximations limiting the size of the system, to fundamental approximations to the underlying equations that are required to achieve any solution to them at all. For example, most ab initio calculations make the Born–Oppenheimer approximation, which simplifies the underlying Schrödinger equation by assuming that the nuclei remain in place during the calculation. In principle, ab initio methods converge to the exact solution of the underlying equations as the number of approximations is reduced. In practice, however, it is impossible to eliminate all approximations, residual error remains.
The goal of computational chemistry is to minimize this residual error while keeping the calculations tractable. In some cases, the details of electronic structure are less important than the long-time phase space behavior of molecules; this is the case in conformational studies of protein-ligand binding thermodynamics. Classical approximations to the potential energy surface are used, as they are computationally less intensive than electronic calculations, to enable longer simulations of molecular dynamics. Furthermore, cheminformatics uses more empirical methods like machine learning based on physicochemical properties. One typical problem in cheminformatics is to predict the binding affinity of drug molecules to a given target. Building on the founding discoveries and theories in the history of quantum mechanics, the first theoretical calculations in chemistry were those of Walter Heitler and Fritz London in 1927; the books that were influential in the early development of computational quantum chemistry include Linus Pauling and E. Bright Wilson's 1935 Introduction to Quantum Mechanics – with Applications to Chemistry, Eyring and Kimball's 1944 Quantum Chemistry, Heitler's 1945 Elementary Wave Mechanics – with Applications to Quantum Chemistry, Coulson's 1952 textbook Valence, each of which served as primary references for chemists in the decades to follow.
With the development of efficient computer technology in the 1940s, the solutions of elaborate wave equations for complex atomic systems began to be a realizable objective. In the early 1950s, the first semi-empirical atomic orbital calculations were performed. Theoretical chemists became extensive users of the early digital computers. One major advance came with the 1951 paper in Reviews of Modern Physics by Clemens C. J. Roothaan in 1951 on the "LCAO MO" approach, for many years the second-most cited paper in that journal. A detailed account of such use in the United Kingdom is given by Smith and Sutcliffe; the first ab initio Hartree–Fock method calculations on diatomic molecules were performed in 1956 at MIT, using a basis set of Slater orbitals. For diatomic molecules, a systematic study using a minimum basis set and the first calculation with a larger basis set were published by Ransil and Nesbet in 1960; the first polyatomic calculations using Gaussian orbitals were performed in the late 1950s.
The first configuration interaction calculations were performed in Cambridge on the EDSAC computer in the 1950s using Gaussian orbitals by Boys and coworkers. By 1971, when a bibliography of ab initio calculations was published, the largest molecules included were naphthalene and azulene. Abstracts of many earlier developments in ab initio theory have been published by Schaefer. In 1964, Hückel method calculations of molecules, ranging in complexity from butadiene and benzene to ovalene, were generated on computers at Berkeley and Oxford; these empirical methods were replaced in the 1960s by semi-empirical methods such as CNDO. In the early 1970s, efficient ab initio computer programs such as ATMOL, Gaussian
American Chemical Society
The American Chemical Society is a scientific society based in the United States that supports scientific inquiry in the field of chemistry. Founded in 1876 at New York University, the ACS has nearly 157,000 members at all degree levels and in all fields of chemistry, chemical engineering, related fields, it is the world's largest scientific society by membership. The ACS is a 501 non-profit organization and holds a congressional charter under Title 36 of the United States Code, its headquarters are located in Washington, D. C. and it has a large concentration of staff in Ohio. The ACS is a leading source of scientific information through its peer-reviewed scientific journals, national conferences, the Chemical Abstracts Service, its publications division produces 60 scholarly journals including the prestigious Journal of the American Chemical Society, as well as the weekly trade magazine Chemical & Engineering News. The ACS holds national meetings twice a year covering the complete field of chemistry and holds smaller conferences concentrating on specific chemical fields or geographic regions.
The primary source of income of the ACS is the Chemical Abstracts Service, a provider of chemical databases worldwide. The organization publishes textbooks, administers several national chemistry awards, provides grants for scientific research, supports various educational and outreach activities. In 1874, a group of American chemists gathered at the Joseph Priestley House to mark the 100th anniversary of Priestley's discovery of oxygen. Although there was an American scientific society at that time, the growth of chemistry in the U. S. prompted those assembled to consider founding a new society that would focus more directly on theoretical and applied chemistry. Two years on April 6, 1876, during a meeting of chemists at the University of the City of New York the American Chemical Society was founded; the society received its charter of incorporation from the State of New York in 1877. Charles F. Chandler, a professor of chemistry at Columbia University, instrumental in organizing the society said that such a body would “prove a powerful and healthy stimulus to original research, … would awaken and develop much talent now wasting in isolation, … members of the association into closer union, ensure a better appreciation of our science and its students on the part of the general public.”Although Chandler was a choice to become the society's first president because of his role in organizing the society, New York University chemistry professor John William Draper was elected as the first president of the society because of his national reputation.
Draper was a photochemist and pioneering photographer who had produced one of the first photographic portraits in 1840. Chandler would serve as president in 1881 and 1889. In the ACS logo designed in the early 20th century by Tiffany's Jewelers and used since 1909, a stylized symbol of a kaliapparat is used; the Journal of the American Chemical Society was founded in 1879 to publish original chemical research. It was the first journal published by ACS and is still the society's flagship peer-reviewed publication. In 1907, Chemical Abstracts was established as a separate journal, which became the Chemical Abstracts Service, a division of ACS that provides chemical information to researchers and others worldwide. Chemical & Engineering News is a weekly trade magazine, published by ACS since 1923; the society adopted a new constitution aimed at nationalizing the organization in 1890. In 1905, the American Chemical Society moved from New York City to Washington, D. C. ACS was reincorporated under a congressional charter in 1937.
It was granted by the U. S. Congress and signed by president Franklin D. Roosevelt. ACS's headquarters moved to its current location in downtown Washington in 1941. Notable Presidents of the American Chemical Society ACS first established technical divisions in 1908 to foster the exchange of information among scientists who work in particular fields of chemistry or professional interests. Divisional activities include organizing technical sessions at ACS meetings, publishing books and resources, administering awards and lectureships, conducting other events; the original five divisions were 1) organic chemistry, 2) industrial chemists and chemical engineers, 3) agricultural and food chemistry, 4) fertilizer chemistry, 5) physical and inorganic chemistry. As of 2016, there are 32 technical divisions of ACS; this is the largest division of the Society. It marked its 100th Anniversary in 2008; the first Chair of the Division was Edward Curtis Franklin. The Organic Division played a part in establishing Organic Syntheses, Inc. and Organic Reactions, Inc. and it maintains close ties to both organizations.
The Division's best known activities include organizing symposia at the biannual ACS National Meetings, for the purpose of recognizing promising Assistant Professors, talented young researchers, outstanding technical contributions from junior-level chemists, in the field of organic chemistry. The symposia honor national award winners, including the Arthur C. Cope Award, Cope Scholar Award, James Flack Norris Award in Physical Organic Chemistry, Herbert C. Brown Award for Creative Research in Synthetic Methods; the Division helps to organize symposia at the international meeting called Pacifichem, it organizes the biennial National Organic Chemistry Symposium which highlights recent advances in organic chemistry and hosts the Roger Adams Award address. The Division organizes corporate sponsorships to provide fellowships for Ph. D. stu
Montreal is the most populous municipality in the Canadian province of Quebec and the second-most populous municipality in Canada. Called Ville-Marie, or "City of Mary", it is named after Mount Royal, the triple-peaked hill in the heart of the city; the city is centred on the Island of Montreal, which took its name from the same source as the city, a few much smaller peripheral islands, the largest of, Île Bizard. It has a distinct four-season continental climate with cold, snowy winters. In 2016, the city had a population of 1,704,694, with a population of 1,942,044 in the urban agglomeration, including all of the other municipalities on the Island of Montreal; the broader metropolitan area had a population of 4,098,927. French is the city's official language and is the language spoken at home by 49.8% of the population of the city, followed by English at 22.8% and 18.3% other languages. In the larger Montreal Census Metropolitan Area, 65.8% of the population speaks French at home, compared to 15.3% who speak English.
The agglomeration Montreal is one of the most bilingual cities in Quebec and Canada, with over 59% of the population able to speak both English and French. Montreal is the second-largest French-speaking city in the world, after Paris, it is situated 258 kilometres south-west of Quebec City. The commercial capital of Canada, Montreal was surpassed in population and in economic strength by Toronto in the 1970s, it remains an important centre of commerce, transport, pharmaceuticals, design, art, tourism, fashion, gaming and world affairs. Montreal has the second-highest number of consulates in North America, serves as the location of the headquarters of the International Civil Aviation Organization, was named a UNESCO City of Design in 2006. In 2017, Montreal was ranked the 12th most liveable city in the world by the Economist Intelligence Unit in its annual Global Liveability Ranking, the best city in the world to be a university student in the QS World University Rankings. Montreal has hosted multiple international conferences and events, including the 1967 International and Universal Exposition and the 1976 Summer Olympics.
It is the only Canadian city to have held the Summer Olympics. In 2018, Montreal was ranked as an Alpha− world city; as of 2016 the city hosts the Canadian Grand Prix of Formula One, the Montreal International Jazz Festival and the Just for Laughs festival. In the Mohawk language, the island is called Tiohtià:ke Tsi, it is a name referring to the Lachine Rapids to the island's Ka-wé-no-te. It means "a place where nations and rivers unite and divide". In the Ojibwe language, the land is called Mooniyaang which means "the first stopping place" and is part of the seven fires prophecy; the city was first named Ville Marie by European settlers from La Flèche, or "City of Mary", named for the Virgin Mary. Its current name comes from the triple-peaked hill in the heart of the city. According to one theory, the name derives from mont Réal,. A possibility by the Government of Canada on its web site concerning Canadian place names, is that the name was adopted as it is written nowadays because an early map of 1556 used the Italian name of the mountain, Monte Real.
Archaeological evidence demonstrates that First Nations native people occupied the island of Montreal as early as 4,000 years ago. By the year AD 1000, they had started to cultivate maize. Within a few hundred years, they had built fortified villages; the Saint Lawrence Iroquoians, an ethnically and culturally distinct group from the Iroquois nations of the Haudenosaunee based in present-day New York, established the village of Hochelaga at the foot of Mount Royal two centuries before the French arrived. Archeologists have found evidence of their habitation there and at other locations in the valley since at least the 14th century; the French explorer Jacques Cartier visited Hochelaga on October 2, 1535, estimated the population of the native people at Hochelaga to be "over a thousand people". Evidence of earlier occupation of the island, such as those uncovered in 1642 during the construction of Fort Ville-Marie, have been removed. Seventy years the French explorer Samuel de Champlain reported that the St Lawrence Iroquoians and their settlements had disappeared altogether from the St Lawrence valley.
This is believed to be due to epidemics of European diseases, or intertribal wars. In 1611 Champlain established a fur trading post on the Island of Montreal, on a site named La Place Royale. At the confluence of Petite Riviere and St. Lawrence River, it is where present-day Pointe-à-Callière stands. On his 1616 map, Samuel de Champlain named the island Lille de Villemenon, in honour of the sieur de Villemenon, a French dignitary, seeking the viceroyship of New France. In 1639 Jérôme Le Royer de La Dauversière obtained the Seigneurial title to the Island of Montreal in the name of the Notre Dame Society of Montreal to establish a Roman Catholic mission to evangelize natives. Dauversiere hired Paul Chomedey de Maisonneuve 30, to lead a group of colonists to build a mission on his new seigneury; the colonists left France in 1641 for Quebec, arrived on the island the following year. On May 17, 1642, Ville-Marie was founded on the southern shore of Montreal is