The Hungarian Reformed Church in America is a mainline Reformed Protestant church in the United States that serves people of Hungarian ancestry. The church has approximately 6,080 members.

History
After World War I, Hungarian people began to come to the United States. They established churches which were under the control of the Reformed Church in their home country. In 1921, an agreement was made to be part of the American Reformed churches. This was the Tiffini Agreement. One part of these churches accepted this - today this is the Calvin Synod of the United Church of Christ - but not all accepted the Tiffini Agreement. Dr Zoltan Kuthy, a dean in New York, and Rev. Endre Sebestyén dreamed of a separate Hungarian Reformed Church. This effort was widely supported. Independent Hungarian churches separated from these churches. The first was the Independent Hungarian Reformed Church in Dubuque, Pennsylvania in 1924. The Independent Hungarian Reformed Church in America was formed. Five pastors signed the creation of this new denomination, Rev. Lajos Nánássy, Perth Amboy, NJ, Mihály Kovács, Detroit, MI, Endre Sebestyén, Duquesne, PA, Károly Vincze, Carteret, NJ, György Borsy-Kerekes, McKeesport, PA. In Dubuque they established a Presbytery. The dean was Endre Sebestyén, the janitor was István Bodnár. Sister church relations was established with the Hungarian Reformed Church.

In 1928 a General Assembly was held in Trenton, NJ and a second presbytery was created, this time the denomination consisted of 17 congregations and 12 pastors. The church had a newspaper, founded in 1921, this was the Hungarian Church (Magyar Egyház - in Hungarian) The present name was adopted in 1958. The church follows the Hungarian model and elects a Bishop, and Deans for its three classes. They hold Synod meetings in every four years.

Statistics
Today there are 23 congregations, 11 mission churches, and 24 pastors.

Recent issues
The Hungarian Reformed community in America was refreshed by the refugees fleeing the Soviet crushing of the abortive revolution of 1956. Although the Hungarian Reformed Church in America has faced ageing and declining memberships, the church has more recently opened several new mission churches.

The Hungarian Reformed Church in America applied for membership in the Reformed Church in Hungary in May 2009. Later the Hungarian Reformed Church in America voted to join the Reformed Church in Hungary. In the same year the church celebrated its 85th anniversary.

Theology
 Apostles Creed
 Nicene Creed
 Heidelberg Catechism
 Second Helvetic Confession

Congregations
See Hungarian congregations across the US www.hungariancatholicmission.com/faith/otherhungariandenominations-us.htm
American Hungarian Reformed Church (Allen Park, Michigan)
Free Magyar Reformed Church of San Francisco & Vicinity (Redwood City, California)

References

External links
Hungarian Reformed Church in America
Calvin Synod
Reformatus

Reformed denominations in the United States
Members of the World Communion of Reformed Churches
Christian organizations established in 1924
Hungarian Reformed organizations in North America
Hungarian-American culture

Hungarian Reformed Church in America


Laurussia was a minor supercontinent which formed in the Devonian period. It is often called the Old Red Sandstone Continent or Euramerica.

Laurussia included much of what is now northern Europe, Greenland and North America.

Lifespan

Laurussia formed when 3 continents Baltica, North America, and Avalonia collided with each other during the Silurian. Baltica and Avalonia collided with each other first in the Shelveian Phase of the Caledonian orogeny. Then Avalonia and Baltica collided with North America in the Acadian Phase of the Caledonian orogeny. This drift of Avalonia closed the Iapetus Ocean and opened the Rheic Ocean behind it.

Laurussia became part of Pangaea in the Permian. In the Jurassic, when Pangaea rifted into two supercontinents, Gondwana and Laurasia, Laurussia became part of Laurasia. The Atlantic ocean opened up in the middle of Laurussia, causing it to split into North America and Europe.

Supercontinents

Laurussia


Android 18 is a female character in the manga series Dragon Ball and the anime Dragon Ball Z. She is an android created by Dr. Gero to kill Goku.

Physical appearance
Android 18 is a beautiful blonde woman of average height and build she has blue eyes, and wears golden hoop earrings in both ears when she first appeared in Dragon Ball Z she wears a blue demin and skirt with a RR (Red Ribbon) logo. She also wears dark blue tights, a brown belt, brown boots and a black skirt that has white and black striped long sleeve. After the defeat of Cell she wears pale blue buttoned up demin vest, white jeans, red hoop earrings along with a red bracelet on her left hand and black flip flops.

Background
Android 18 was originally a human along with her twin brother Android 17. She and her brother 17 were delinquents until the scientist Dr. Gero kidnapped them and reconstruct them into superhumans (androids).

Character role
Android 18's personally and behavior is calm, cool and confident and is somewhat sarcastic. During her early appearances in Dragon Ball Z she was somewhat arrogant usually getting annoyed by her brother Android 17's wild teen like behavior. She was also hotheaded when she refused to run away from her brother and Android 16 when Cell threatened to absorb her. After the defeat of Cell, Android 18 is calmer and is married to Krillin and they have a daughter named Marron and she is a good mother to her daughter. She was usually seen with Piccolo and other Z Fighters on Kami's lookout during the Majin Buu threat. Android 18 also appears in Dragon Ball GT and Super. In Dragon Ball GT she is seen with her husband Krillin and daughter Marron when one day her twin brother Android 17 arrives and attempt to control 18, 17 also kill Krillin which greatly infuriated Android 18 and she attacks her brother however Android 17 attacks her with an energy blast injuring 18. Android 18 is later seen in GT confronting now Super Android 17 about killing her husband and injuring her 18 then distracts Super 17 with multiple energy attacks which allows Goku to kill Super 17. After Super 17's defeat Android 18 is seen crying about her husband's death and then tells Goku that he a great friend and ally. Android 18 also appears in Dragon Ball Super as a side character when the God of Destruction Beerus threatens to destroy the Earth she and the Z Fighters attacks Beerus attempting to defeat Beerus but failed to defeat him by him overpowering them before Goku arrives to save them. Android 18 is in the Universal Survival Arc, she is on Team Universe 7 alongside her husband Krillin,  her twin brother Android 17 and the other Z-Fighters.

In other media
Android 18 appears in several Dragon Ball Z movies and videos games. She appears in Dragon Ball movies like Super Android 13 , Bio-Broly, Battle of Gods, Resurrection F and in video games like Dragon Ball Z Budokai Tenkaichi series, Dragon Ball Z Raging Blast 1 and 2 etc.

Dragon Ball characters

Android 18 (Dragon Ball)


The Adventist Church of Promise ( or "IAP") is an evangelical Christian denomination which is both Sabbatarian Adventist and classical Pentecostal in its doctrine and worship. It was founded in Brazil in 1932 by pastor John August Silveira (Portuguese João Augusto da Silveira), as a split-off from the Seventh-day Adventist Church.

It is the second-largest Adventist denomination in South America (after the Seventh-day Adventist Church). It claims to be the first indigenous Brazilian Pentecostal denomination. (The earlier Assemblies of God in Brazil were introduced from the United States). Most of the church members live in Brazil, yet the church is also present in other countries: Argentina, Paraguay, Chile, Bolivia, Colombia, El Salvador, United States, Portugal, Spain, Nigeria, Mozambique, Cameroon and Uruguay. Worldwide there are approximately 200,000 Adventists of Promise.

Beliefs
The Adventist Church of Promise believes in:

 Verbal inspiration of the Bible, sola scriptura and inerrancy of the Bible,
 Trinity: Father, Son and Holy Spirit,
 Virgin birth of Jesus Christ, substitutionary atonement on the cross, resurrection and ascension of Jesus,
 Jesus Christ as the only Saviour and only mediator between God and men,
 Justification is only by grace through faith, not by works,
 Experience of new birth or acceptance of Jesus as a personal Lord and Savior is absolutely necessary for salvation,
 Water baptism by immersion must be preceded by personal repentance and faith in the gospel,
 Baptism with the Holy Spirit is another blessing for those who believed,
 Initial evidence of the baptism with the Holy Spirit is always speaking with other tongues,
 Holy living, sanctification and obeying Ten Commandments is consequence of receiving salvation,
 Difference between ceremonial and moral laws of God; the moral law (Ten Commandments) is still valid for all Christians,
 The Seventh-day Sabbath, blessed and sanctified by God after creation, is still the holy day of rest and worship,
 Supernatural spiritual gifts (tongues, prophecy etc.) are as widespread as in the first century,
 Divine healing and all of the apostolic era signs are still available for the Church today,
 Christian temperance includes full abstinence from all alcoholic drinks, tobacco and unclean foods,
 Three ordinances of Christ: water baptism of repentant sinners, Lord's Supper and washing of feet,
 Marriage between one man and one woman,
 Death is unconscious sleep until the resurrection (conditional immortality),
 Very soon premillennial second coming of Christ,
 Millennial Kingdom of Christ with saints in heaven,
 Postmillennial Great White Throne Judgment, annihilation of the wicked and restoration of the Earth to paradise.

See also
 Charismatic Adventism

References

Further reading
 História Documental do Protestantismo no Brasil, ASTE, 1984, p379
 Eugene Lincoln, in The Sabbath Sentinel April 1978, (Cleveland, Tennessee: Bible Sabbath Association), p6
 "The Sabbath in the New World" by Raymond Cottrell, p244–263 of The Sabbath in Scripture and History ed. Kenneth Strand. Brief mention on p255, referencing Lincoln above
 "Why Historic Churches Are Declining and Pentecostal Churches Are Growing in Brazil" by Leonildo Silveira C., in In the power of the Spirit: The Pentecostal Challenge to Historic Churches in Latin America ed. Benjamin F. Gutiérrez and Dennis A. Smith. Presbyterian Church (U.S.A.), Worldwide Ministries Division. Brief mention
 "Workbook on Intercultural Pastoral Care and Counselling" by Karl Federschmidt, Klaus Temme and Helmut Weiss. Düsseldorf, Germany: (Published for the ) Society for Intercultural Pastoral Care and Counselling, 2004. Brief mention on p83

External links

Seventh-day denominations
Charismatic Adventism
Protestant churches in Brazil
Pentecostal churches in Brazil
Adventist organizations established in the 20th century
Pentecostal denominations established in the 20th century
Christian organizations established in 1932

Adventist Church of Promise


Hans-Hubert Schönzeler (22 June 192530 April 1997) was a German-born Australian-naturalised English-resident composer, conductor and musicologist who became an authority on Anton Bruckner and Antonín Dvořák.

He was born in Leipzig, an only child, and studied the violin from the age of five. Although his family was not Jewish, he was sent to Brussels so as to avoid contact with the Hitler Youth. In 1939 his family emigrated to Australia where, on the outbreak of the Second World War, his father was interned as an enemy alien. Hans-Hubert went to Sydney Boys High School, but in 1941 he and his mother were also interned for the duration of the war. During these years he continued to study music.  He also studied conducting with a former director of the Vienna Boys' Choir. He was released in 1946 and was naturalised as an Australian in 1947. He attended the New South Wales State Conservatorium, where he studied with Eugene Goossens.

With assistance from Rafael Kubelík, Schönzeler settled in London in 1950, and went to work for Eulenburg Editions.  He was later a director of the company. He conducted the 20th-Century Ensemble in London from 1951 to 1962.  He studied at the Paris Conservatoire and the Accademia Musicale Chigiana in Siena, and worked as a freelance conductor in many countries as well as the UK.  He conducted the concert at the Royal Albert Hall in 1964 marking the 10th anniversary of the death of Wilhelm Furtwängler, whose biography he later wrote.  In 1967 he commenced a long association with the West Australian Symphony Orchestra.

Schönzeler became a noted expert on Bruckner: in 1970 he wrote a book on the composer; in 1973 he conducted the world premiere of the first version of the Eighth Symphony; at the 1978 Adelaide Festival he conducted the world premiere of the authentic first version of the Third Symphony. He was honoured by the International Bruckner Society, Vienna, the Bruckner Society of America and he also won the Bruckner Medal of Honor.

He was also a keen performer of the works of Dvořák; as well as writing a biography, he appeared at the Prague Spring Festival in 1974 and was made an honorary member of the Antonín Dvořák Society in 1975.  He also edited symphonies by Joseph Haydn and Carl Maria von Weber.

His recorded legacy includes works by Bruckner, Edmund Rubbra, Sir Arthur Bliss, Mozart and Beethoven.

Hans-Hubert Schonzeler died in England in 1997.

Selected compositions
 Sonata for viola and piano, Op.5 (1975)
 Tristesse, 5 Songs on texts by Paul Verlaine for voice and piano or string orchestra

References

Sources

Robert Ponsonby Obituary: Hans-Hubert Schonzeler The Independent May 8, 1997

1925 births
1997 deaths
Anton Bruckner
Australian male composers
Australian composers
Australian conductors (music)
Australian musicologists
Naturalised citizens of Australia
Accademia Musicale Chigiana alumni
Sydney Conservatorium of Music alumni
German emigrants to Australia
20th-century conductors (music)
20th-century Austrian composers
20th-century Austrian male musicians
20th-century musicologists
People interned during World War II
20th-century Australian male musicians
20th-century Australian musicians
Prisoners and detainees of Australia

Hans-Hubert Schönzeler


A Noble family is a family who are related to the Royal family, but they are ranks below King. Nobles usually are less known then Royals but in some cases nobles were more well known. Some "Noble families" are not noble. Take the Medici family and the Borgias.Thoes to family's are known as Banking families and aristocrats. Those families are Rich but not a member of Nobility that is recognized by the King/Emperor.

History
Nobles were always recognized as lower families of the King/Queen. Nobles usually ruled Duchy's, Counties, and principalities. Nobles were usually given a "House" which was of course a noble house. Nobles usually worked as advisors to the King, and land owners. But some families did not work at all because they were really rich. But not all nobles were rich. Some Nobles were very poor. One of the richest claim to be noble families were the Medicis. The Medici's ruled Tuscany, Milan ect. The Medici's were pretty much common people, but they were richer than most monarchs at there time until there fall in the 1700's. One of the poorest family's were a period of time was the Bonaparte family. They were poor until Napoleon became Emperor of the French.

Power
Noble families had plenty of power depending on what land they ruled. The rich Duchy of Burgundy was a major power spot because of how big to Duchy was. Another power spot was the Duchy of Milan and the Duchy of Luxembourg. But some Nobles had little to no power. Mostly because most nobles are given an style like "Lady" that is non hereditary.

Famous Noble Families

 House of Boleyn
 House of Grey
 House of Bourbon
 House of Normandy
 House of Foix
 House of Hesse
 House of Nassu

Noble families

Noble Family


Santa Cristina is a Baroque style, Roman Catholic church located in Turin, region of Piedmont, Italy. It mirrors the adjacent church of San Carlo and faces the Piazza San Carlo. The arrangement recalls the twin churches (chiese gemelle) of Santa Maria dei Miracoli (1681) and Santa Maria in Montesanto (1679) facing the Piazza del Popolo in Rome.

History
The original layout was designed in 1620 by the architect Carlo di Castellamonte, and construction pursued until 1639. The project was only completed between 1715 and 1718, under the guidance of Filippo Juvarra, including the facade elaborately decorated with ovals and details with statues of saints and allegories of the virtues. The adjacent convent housed nuns of the Order of the Discalced Carmelites. In 1802, the order was suppressed in Turin by Napoleonic forces. The interiors were modified in the 19th-century and after the bombardments of World War II.

References

Roman Catholic churches in Turin
Baroque architecture in Turin
17th-century Roman Catholic church buildings in Italy
Filippo Juvarra buildings

Santa Cristina, Turin


Kincraig Camanachd Club is a shinty team from Kincraig, Badenoch, Scotland. The club's only team withdrew from North Division 3 in 2007 due to a lack of players, but re-entered the league in 2008, however Kincraig withdrew yet again in 2009. The club is currently abeyance at senior level as of 2010.   As of 2014, the club has started redeveloping its senior side with an aim to re-enter the leagues in the future. The club is also notable for providing at least three Olympians for Great Britain.

History

Formed in 1920 after the amalgamation of Alvie and Insh Shinty Clubs, Kincraig have gained the reputation as the third team in Badenoch due to its proximity to Kingussie and Newtonmore. The club was traditionally a good outlet for players who could not get a game for either club, but in recent years this supply dried up.

The club went into abeyance in 1955 but restarted in 1972. Olympic skiers Alain Baxter, Noel Baxter and Andrew Freshwater all played regularly for the club in the past.  Ronald Ross is originally from the Kincraig area.

The club won the Sir William Sutherland Cup in 2001, its first National silverware.

The club again went into abeyance during season 2007 with committee members blaming a lack of cooperation from Kingussie and Newtonmore in loaning them youth players.

The club applied late for the 2008 season but were allowed into the league at short notice.  They competed well in 2008 and 2009 saw them start the season but they encountered severe team raising difficulties in the second half of the season which resulted in them withdrawing from North Division Three.  The club is again went into abeyance at senior level but aims for re-entry to senior shinty in 2010 were dashed after a poor turnout at the AGM.   President Dennis Meldrum was hopeful that there would be a return to senior shinty sooner rather than later.

In 2011, a team based in the Grantown-on-Spey area, called Strathspey Camanachd, arose. Several players formerly with Kincraig moved to Strathspey in 2012. However, in 2013 Kincraig showed signs of recovery with a few friendlies and a visit to Lewis. They did not return to league shinty in 2014, but continue to develop their youth system, with the aim of entering in 2015.

References

External links
Kincraig Community Website
Kincraig fold
Kincraig restart

Shinty teams
1920 establishments in Scotland
Sport in Highland (council area)
Badenoch and Strathspey
Sports clubs and teams established in 1920

Kincraig Camanachd Club


Whacky was a British comic strip published in the British comic book magazine Cor!! and ran in the comic from its first issue on 6 June 1970 until 29 September 1973 - some 9 months before it was merged with Buster. It started as a half page strip but proved popular and was given a full page several weeks later. It was created and drawn by Mike Lacey.

Concept

The strip is about a fictional schoolboy called Whacky who is regularly being whacked (slang for "beating" or "thrashing") - later issues used the tag-line "He's always getting whacked" to emphasise the point. Most of the strips were school based and involved Whacky getting into trouble with his sadistic teacher Mr Thwackery - while these situations would typically involve lateness, talking in class etc., many times his teacher would find any excuse for regularly punishing him (even if Whacky is not at fault), which he often noticeably revelled in. His punishments were mostly the traditional "six of the best" with the cane - though in its absence other items would be used including an umbrella, slipper, plank, tree branch, walking stick, plimsoll, stick of rock, belt and book! At the time, the cane was still used in many British schools and coincided with the revival of the Jimmy Edwards TV show Whacko so this sort of behaviour was deemed perfectly innocent, as were the regular slipperings that Dennis The Menace received.

In one strip Whacky reasons how he got his name: that when he was first born the nurse smacked him on his rear!

The character was typically dressed as an old fashioned schoolboy: blazer (when in colour it would either be green, orange or red), matching cap, shirt and tie and school shorts, even in the winter. When not at school he usually wore a sweater; however, he still sported his school uniform shorts. He also carried the obligatory satchel to school.

The strip ended in the comic in 1973 with Mr. Thwackery's retirement. A jubilant Whacky races out of school, convinced he will not be punished any more, but on the way home he kicks a football into his new neighbour's garden - who happens to be Mr. Thwackery. He duly chases the lad over fences, cane in hand, with Whacky exclaiming "Will it never end...?"

Continuation

The strip continued in the Cor!! summer specials and annuals that were still published into the early 1980s finishing with an appearance in the 1984 annual (published Christmas 1983) where Whacky walks into school to be greeted by a sign on the noticeboard exclaiming "No Whackings allowed" - mirroring real life as corporal punishment was being banned in England. Mr. Thwackery manages to punish Whacky "by accident" (opening a door onto him and dropping a desk lid on him as he is bent over) before he manages to whack the headmaster by mistake. The final frame showing Mr. Thwackery being whacked by the headmaster, with Whacky watching on...!

Sources

British comic strips
1970 comics debuts
1973 comics endings
Child characters in comics
Comics about children
British comics characters
Comics characters introduced in 1970
Gag-a-day comics
School-themed comics

Whacky


Francisco de Orellana Bejarano Pizarro y Torres de Altamirano (; 1511 – November 1546) was a Spanish explorer and conquistador. In one of the most improbably successful voyages in known history, Orellana managed to sail the length of the Amazon, arriving at the river's mouth on 24 August 1542. He and his party sailed along the Atlantic coast until reaching Cubagua Island, near the coast of Venezuela.

Orellana founded the city of Guayaquil in what is now Ecuador, and died during a second expedition on the Amazon.

Background
Born in Trujillo, Caceres (various birth dates, ranging from 1490 to 1511, are still quoted by biographers), Orellana was a close friend and possibly a relative of Francisco Pizarro, the Trujillo-born conquistador of Peru (his cousin, according to some historians). He traveled to the New World (probably in 1527). Orellana served in Nicaragua until joining Pizarro's army in Peru in 1533, where he supported Pizarro in his conflict with Diego de Almagro (1538). After the victory over De Almagro's men, he was appointed governor of La Culata. He re-established the town of Guayaquil, previously founded by Pizarro and repopulated by Sebastián de Belalcázar.
(During the civil war, he sided with the Pizarros and was Ensign General of a force sent by Francisco Pizarro from Lima to aid Hernando Pizarro. He was granted land at Puerto Viejo, on the coast of Ecuador.)

First exploration of the Amazon River

In 1540 Gonzalo Pizarro arrived in Quito as vice governor and was charged by Francisco Pizarro, his older paternal half-brother, with an expedition to locate the "Land of Cinnamon", thought to be somewhere to the east. Orellana was one of Gonzalo Pizarro's lieutenants during his 1541 expedition east of Quito into the South American interior. In Quito, Gonzalo Pizarro collected a force of 220 Spaniards and 4000 natives. At the same time, as second in command, Orellana was sent back to Guayaquil to gather troops and horses. Pizarro left Quito in February 1541, just before Orellana arrived with his 23 men and horses. Orellana hurried after the main expedition, eventually contacting them in March. However, by the time the expedition had left the mountains, 3000 natives and 140 Spanish had died or deserted.

On reaching the River Coca (a tributary of the Napo), a brigantine, the San Pedro, was constructed to ferry the sick and supplies. Gonzalo Pizarro ordered him to explore the Coca River and return after finding the river's end. When they arrived at the confluence with the Napo River, his men threatened to mutiny if they did not continue. On 26 December 1541, he agreed to be elected chief of the new expedition and conquer new lands in the king's name. Orellana (with the Dominican Gaspar de Carvajal who chronicled the expedition) and 50 men set off downstream to find food. Unable to return against the current, Orellana waited for Pizarro, finally sending back three men with a message, and started constructing a second brigantine, the Victoria. Pizarro had in the meantime returned to Quito by a more northerly route, by then with only 80 men left alive.

After leaving the village on the Napo, Orellana continued downstream to the Amazon. The 49 men began to build a bigger ship for river navigation. During their navigation on Napo River, they were threatened constantly by the Omaguas. They reached the Negro River on 3 June 1542 and finally arrived on the Amazon River.

At a longitude of about 69°W, Orellana and his men were involved in a skirmish with Machiparo's natives and were chased downstream. Continuing downstream, they consecutively passed the Rio de la Trinidad (possibly the Rio Juruá), the Pueblo Vicioso, the Rio Negro (named by Orellana), the Pueblo del Corpus, the Pueblo de los Quemados, and the Pueblo de la Calle at about 57°W. There they entered the territory of the Pira-tapuya.

The name 'Amazon' is said to arise from a battle Francisco de Orellana fought with a tribe of Tapuyas. The women of the tribe fought alongside the men, as was the custom among the tribe. Orellana described the river as "the river of the Amazons", referring to the mythical Amazons of Asia described by Herodotus (see The Histories [4.110–116]) and Diodorus in Greek legends. A skirmish with these South American warrior women reportedly took place on 24 June 1542 while Orellana was approaching the Trombetus River, in the neighborhood of the  at the junction with the River Madeira.

At about 54°W, they stopped for 18 days to repair the boats and finally reached the open sea on 26 August 1542, and checked the boats for seaworthiness. While coasting toward Guiana, the brigs were separated until reunited at Nueva Cadiz on Cubagua island off the coast of Venezuela. The Victoria, carrying Orellana and Carvajal, passed south around Trinidad and was trapped in the Gulf of Paria for seven days, finally reaching Cubagua on 11 September 1542. The San Pedro sailed north of Trinidad and reached Cubagua on 9 September.

Second expedition and death

Preparations
From Cubagua, Orellana decided to return to Spain to obtain from the Crown the governorship over the discovered lands, which he named New Andalusia. After a difficult navigation, he touched first the shores of Portugal. The king received him in a friendly way and made him an offer to go back to the Amazon under a Portuguese flag. Orellana's exploration produced an international issue. According to the Treaty of Tordesillas, the majority of the Amazon River should belong to Spain. However, the mouth should be ruled by Portugal. Orellana refused the Portuguese offer and went to Valladolid.

After nine months of negotiations, Charles I appointed him governor of New Andalusia on February 18, 1544. After captivating the Spanish court with tales and alleged exaggerations of his voyage down the Amazon, Orellana obtained a commission to conquer and settle Nueva Andalucia. The charter established that he should explore and settle the Amazonian lands with 300 men and 100 horses, and found two cities, one in the mouth and another in the basin's interior, Manaus.

The commission was accepted on 18 February 1544. However, preparations for the voyage were frustrated by unpaid debts, Portuguese spies, and internal wranglings. Sufficient funds were raised through the efforts of Cosmo de Chaves, Orellana's stepfather. However, the problems were compounded by Orellana's decision to marry a very young and poor girl, Ana de Ayala, whom he intended to take with him (along with her sisters). Orellana's creditors relented and allowed him to sail only on the arrival of a Portuguese spy fleet at Seville. On reaching Sanlucar he was detained again, the authorities having discovered a shortfall in his complement of men and horses, and that large numbers of his crew were not Spanish. On 11 May 1545, Orellana (in hiding on one of his vessels) surreptitiously sailed out of Sanlucar with four ships and disappeared from view.

Expedition
On 11 May 1545, he left Spain with four ships, supplies to build two riverboats, perhaps 300 men, at least 24 horses, and his young wife. Before leaving land, he looted a farm for cattle, pigs, and chickens, which he salted.  In the open sea, he waylaid a caravel and looted its supplies. At the end of May, he reached Tenerife and spent three months there putting his ships in order. He then sailed to the Cape Verde Islands where an epidemic killed 98 of his men and 50 or 60 deserted.  With this loss, he abandoned one of his ships after salvaging what he could. He left about the middle of November. The crossing was difficult, and one of his ships became separated and was never seen again. With it went 77 men, 11 horses, and supplies to build one riverboat.  He lost several anchors and had to replace them with cannons.

He reached the Brazil coast, sailed a hundred leagues until he found fresh water in the sea, which he assumed came from the Amazon. He landed on 20 December 1545 with two ships, 11 thin horses, and perhaps 100 men.  Since the natives were friendly and there was plenty of food, his men suggested that they stop and rest and build the riverboat. Orellana overruled them and set off to find the main branch of the Amazon five days later. After sailing more than 300 miles he made camp and started building the riverboat. This took from January to March. They were forced to cannibalize the smaller of the two ships. The natives were hostile, there was little food in the area, and they had to eat all their dogs and horses. Fifty-seven men died.

Orellana sent the newly-built boat off to find food, but it returned with no food and several men dead of hunger or wounds. He set off with the remaining ship and the riverboat. After traveling 75 miles southeast, the ship was wrecked on a riverbank. Orellana continued with the boat, leaving many men at the shipwreck camp.  After nearly a month, he returned to the shipwreck, reporting that he had gone 500 miles and not found the main river. Orellana was now in poor shape, both physically and mentally. He set off again with the boat. Seventeen of his men were wounded by arrows. According to his wife, he died "from illness and grief." The survivors went downriver to the sea where they were driven by the South Equatorial Current to the Spanish base at Margarita Island west of Trinidad.

After Orellana left the shipwreck camp, the 28 or 30 men there began building a boat from the wrecked ship, which took more than three months. The boat was ill-built and leaky. Some indigenous people guided them to "a place where the Amazon splits into three arms". Finding no sign of Orellana, they went downriver. Ten men jumped ship, preferring life with the natives to a leaking boat. Reaching the sea, the current carried them northwest. In late November, the 18 survivors reached Margarita Island, where they met the other 25 survivors and Orellana's wife.

Documentation of Amazonian civilizations

Orellana's first expedition was chronicled by Gaspar de Carvajal. The BBC documentary Unnatural Histories presents evidence that Carvajal's chronicle, Relación del nuevo descubrimiento del famoso río Grande que descubrió por muy gran ventura el capitán Francisco de Orellana ("Account of the recent discovery of the famous Grand river which was discovered by great good fortune by Captain Francisco de Orellana"), rather than being a hugely exaggerated fantasy as previously thought, was correct in its observations that an advanced civilization was flourishing along the Amazon in the 1540s.

It is believed that the civilization was later devastated by the spread of smallpox and other diseases from Europe. The evidence to support this claim comes from the discovery of numerous geoglyphs dating from between 1 and 1250 AD, and terra preta resulting from indigenous activities. Some five million people may have lived in the Amazon region in 1500 in dense riverbank settlements such as that at Marajó, and inland. By 1900 the population had fallen to one million, and by the early 1980s it was fewer than 200,000.

Places named after Orellana
Puerto Francisco de Orellana, Ecuador
Orellana Province, Ecuador
Francisco de Orellana, Maynas, Loreto, Peru
 The Amazon River was once called the Orellana River

Historical chronicles
Gaspar de Carvajal, the chaplain of the first expedition, wrote a chronicle Relación del nuevo descubrimiento del famoso río Grande que descubrió por muy gran ventura el capitán Francisco de Orellana (Chronicle of the new discovery of the famous Great river discovered by great good fortune by Captain Francisco de Orellana) which was partly reproduced in Gonzalo Fernández de Oviedo y Valdés's Historia general y natural de las Indias, initially published in 1526 but continually revised until the author's death in 1557, who included in addition statements by Orellana and some of his men. Carvajal's manuscript was published in 1894 by the Chilean historian José Toribio Medina, preceded by a biography of Carvajal, in his book Descubrimiento del río de las Amazonas.

A modern retelling of Orellana and his crew's epic journey, with source material primarily provided by Carvajal, is written in Buddy Levy's River of Darkness.

In popular culture
De Orellana's voyages served as partial inspiration for the film Aguirre, the Wrath of God (1972). An earlier script, penned by director Werner Herzog, also deliberately included De Orellana in the movie, but he was ultimately left out.

De Orellana's role in the search for El Dorado also forms part of the plot of the film Indiana Jones and the Kingdom of the Crystal Skull (2008).

William Ospina's 2008 novel El país de la canela (The Cinnamon Country) includes a novelized version of Orellana's trip.

One of the campaigns of Age of Empires II: The Forgotten is called El Dorado and is about the quest of Francisco de Orellana and Francisco Pizarro to find El Dorado, the legendary Lost City of Gold, thought to be hidden somewhere in the vast Amazon rainforest. The campaign is based on De Orellana's first exploration.

References

Further reading
 Dalby, A., "Christopher Columbus, Gonzalo Pizarro, and the search for cinnamon" in Gastronomica (Spring 2001).
 Levy, Buddy (2011), River of Darkness: Francisco Orellana's Legendary Voyage of Death and Discovery Down the Amazon, New York: Bantam Books.  (popular history)
Medina, José Toribio, The Discovery of the Amazon, 1934 (translation), 1894 (original) (collection of documents relating to Orellana)
 Millar, George. A Crossbowman's Story (Knopf, 1954), fictionalized story of the Orellana expedition
 Smith, A. (1994), Explorers of the Amazon, Chicago: University of Chicago Press.
 Warêgne, Jean-Marie (2014); "Francisco de Orellana découvreur de l'Amazone"; Paris: L'Harmattan.

External links

  "Francisco de Orellana: descubriendo el gran río", article in viajeros.com
 "Birthplace of Francisco de Orellana. Discoverer of the Amazon River."
 The Secrets of El Dorado and the Magic of Terra Preta

1500s births
1540s missing person cases
1546 deaths
16th-century explorers
16th-century Spanish people
Spanish explorers
Explorers of Amazonia
Extremaduran conquistadors
Lost explorers
People from Tierra de Trujillo
People who died at sea
Spanish city founders
Eyepatch wearers

Francisco de Orellana


National Lampoon White Album is an American album of humorous songs and spoken word skits. It was originally released as a vinyl record and cassette tape in 1980, but it was reissued and is still available as a CD. It was written and performed by people associated with  National Lampoon magazine and its related productions.

Most of the tracks were by comedians who were not very well known, but the track Hollywood Gay Alliance (which originally aired on the National Lampoon Radio Hour in 1974) featured John Belushi, Chevy Chase, and Christopher Guest.

The musicians who played on the album were Tony Scheuren (vocals, guitar); Michael Simmons, Rhonda Coullet, Rory Dodd (vocals); Don Sarlin, Steve Burgh (guitar); Harvey Shapiro (steel guitar); Curtis Fields (saxophone); Paul Jacobs, Bruce Foster (keyboards); Barry Lazarowitz, Michael Finkelstein, and Yogi Horton (drums).

Track listing
 Perrier Junkie
 At the Bar
 What is God?
 Fartman
 Discoleptic
 Steak
 The Sounds of Physical Love
 Gay Alliance
 Robert Caucasian vs. Squab
 What about Reupholsterers?
 Shakespeare Knock Knocks
 Nude Figure Model
 Couple at the Door
 Christopher Street
 California Hot Tub
 What Turns Women On
 What Were You Expecting - Rock and Roll?

References

National Lampoon albums
1980 albums
1980s comedy albums

National Lampoon White Album


Folding@home (FAH or F@h) is a distributed computing project aimed to help scientists develop new therapeutics for a variety of diseases by the means of simulating protein dynamics. This includes the process of protein folding and the movements of proteins, and is reliant on simulations run on volunteers' personal computers. Folding@home is currently based at the University of Pennsylvania and led by Greg Bowman, a former student of Vijay Pande.

The project utilizes graphics processing units (GPUs), central processing units (CPUs), and ARM processors like those on the Raspberry Pi for distributed computing and scientific research. The project uses statistical simulation methodology that is a paradigm shift from traditional computing methods. As part of the client–server model network architecture, the volunteered machines each receive pieces of a simulation (work units), complete them, and return them to the project's database servers, where the units are compiled into an overall simulation. Volunteers can track their contributions on the Folding@home website, which makes volunteers' participation competitive and encourages long-term involvement.

Folding@home is one of the world's fastest computing systems. With heightened interest in the project as a result of the COVID-19 pandemic, the system achieved a speed of approximately 1.22 exaflops by late March 2020 and reached 2.43 exaflops by April 12, 2020, making it the world's first exaflop computing system. This level of performance from its large-scale computing network has allowed researchers to run computationally costly atomic-level simulations of protein folding thousands of times longer than formerly achieved. Since its launch on October 1, 2000, Folding@home was involved in the production of 226 scientific research papers. Results from the project's simulations agree well with experiments.

Background

Proteins are an essential component to many biological functions and participate in virtually all processes within biological cells. They often act as enzymes, performing biochemical reactions including cell signaling, molecular transportation, and cellular regulation. As structural elements, some proteins act as a type of skeleton for cells, and as antibodies, while other proteins participate in the immune system. Before a protein can take on these roles, it must fold into a functional three-dimensional structure, a process that often occurs spontaneously and is dependent on interactions within its amino acid sequence and interactions of the amino acids with their surroundings. Protein folding is driven by the search to find the most energetically favorable conformation of the protein, i.e., its native state. Thus, understanding protein folding is critical to understanding what a protein does and how it works, and is considered a holy grail of computational biology. Despite folding occurring within a crowded cellular environment, it typically proceeds smoothly. However, due to a protein's chemical properties or other factors, proteins may misfold, that is, fold down the wrong pathway and end up misshapen. Unless cellular mechanisms can destroy or refold misfolded proteins, they can subsequently aggregate and cause a variety of debilitating diseases. Laboratory experiments studying these processes can be limited in scope and atomic detail, leading scientists to use physics-based computing models that, when complementing experiments, seek to provide a more complete picture of protein folding, misfolding, and aggregation.

Due to the complexity of proteins' conformation or configuration space (the set of possible shapes a protein can take), and limits in computing power, all-atom molecular dynamics simulations have been severely limited in the timescales that they can study. While most proteins typically fold in the order of milliseconds, before 2010, simulations could only reach nanosecond to microsecond timescales. General-purpose supercomputers have been used to simulate protein folding, but such systems are intrinsically costly and typically shared among many research groups. Further, because the computations in kinetic models occur serially, strong scaling of traditional molecular simulations to these architectures is exceptionally difficult. Moreover, as protein folding is a stochastic process (i.e., random) and can statistically vary over time, it is challenging computationally to use long simulations for comprehensive views of the folding process.

Protein folding does not occur in one step. Instead, proteins spend most of their folding time, nearly 96% in some cases, waiting in various intermediate conformational states, each a local thermodynamic free energy minimum in the protein's energy landscape. Through a process known as adaptive sampling, these conformations are used by Folding@home as starting points for a set of simulation trajectories. As the simulations discover more conformations, the trajectories are restarted from them, and a Markov state model (MSM) is gradually created from this cyclic process. MSMs are discrete-time master equation models which describe a biomolecule's conformational and energy landscape as a set of distinct structures and the short transitions between them. The adaptive sampling Markov state model method significantly increases the efficiency of simulation as it avoids computation inside the local energy minimum itself, and is amenable to distributed computing (including on GPUGRID) as it allows for the statistical aggregation of short, independent simulation trajectories. The amount of time it takes to construct a Markov state model is inversely proportional to the number of parallel simulations run, i.e., the number of processors available. In other words, it achieves linear parallelization, leading to an approximately four orders of magnitude reduction in overall serial calculation time. A completed MSM may contain tens of thousands of sample states from the protein's phase space (all the conformations a protein can take on) and the transitions between them. The model illustrates folding events and pathways (i.e., routes) and researchers can later use kinetic clustering to view a coarse-grained representation of the otherwise highly detailed model. They can use these MSMs to reveal how proteins misfold and to quantitatively compare simulations with experiments.

Between 2000 and 2010, the length of the proteins Folding@home has studied have increased by a factor of four, while its timescales for protein folding simulations have increased by six orders of magnitude. In 2002, Folding@home used Markov state models to complete approximately a million CPU days of simulations over the span of several months, and in 2011, MSMs parallelized another simulation that required an aggregate 10 million CPU hours of computing. In January 2010, Folding@home used MSMs to simulate the dynamics of the slow-folding 32-residue NTL9 protein out to 1.52 milliseconds, a timescale consistent with experimental folding rate predictions but a thousand times longer than formerly achieved. The model consisted of many individual trajectories, each two orders of magnitude shorter, and provided an unprecedented level of detail into the protein's energy landscape. In 2010, Folding@home researcher Gregory Bowman was awarded the Thomas Kuhn Paradigm Shift Award from the American Chemical Society for the development of the open-source MSMBuilder software and for attaining quantitative agreement between theory and experiment. For his work, Pande was awarded the 2012 Michael and Kate Bárány Award for Young Investigators for "developing field-defining and field-changing computational methods to produce leading theoretical models for protein and RNA folding", and the 2006 Irving Sigal Young Investigator Award for his simulation results which "have stimulated a re-examination of the meaning of both ensemble and single-molecule measurements, making Pande's efforts pioneering contributions to simulation methodology."

Examples of application in biomedical research
Protein misfolding can result in a variety of diseases including Alzheimer's disease, cancer, Creutzfeldt–Jakob disease, cystic fibrosis, Huntington's disease, sickle-cell anemia, and type II diabetes. Cellular infection by viruses such as HIV and influenza also involve folding events on cell membranes. Once protein misfolding is better understood, therapies can be developed that augment cells' natural ability to regulate protein folding. Such therapies include the use of engineered molecules to alter the production of a given protein, help destroy a misfolded protein, or assist in the folding process. The combination of computational molecular modeling and experimental analysis has the possibility to fundamentally shape the future of molecular medicine and the rational design of therapeutics, such as expediting and lowering the costs of drug discovery. The goal of the first five years of Folding@home was to make advances in understanding folding, while the current goal is to understand misfolding and related disease, especially Alzheimer's.

The simulations run on Folding@home are used in conjunction with laboratory experiments, but researchers can use them to study how folding in vitro differs from folding in native cellular environments. This is advantageous in studying aspects of folding, misfolding, and their relationships to disease that are difficult to observe experimentally. For example, in 2011, Folding@home simulated protein folding inside a ribosomal exit tunnel, to help scientists better understand how natural confinement and crowding might influence the folding process. Furthermore, scientists typically employ chemical denaturants to unfold proteins from their stable native state. It is not generally known how the denaturant affects the protein's refolding, and it is difficult to experimentally determine if these denatured states contain residual structures which may influence folding behavior. In 2010, Folding@home used GPUs to simulate the unfolded states of Protein L, and predicted its collapse rate in strong agreement with experimental results.

The large data sets from the project are freely available for other researchers to use upon request and some can be accessed from the Folding@home website. The Pande lab has collaborated with other molecular dynamics systems such as the Blue Gene supercomputer, and they share Folding@home's key software with other researchers, so that the algorithms which benefited Folding@home may aid other scientific areas. In 2011, they released the open-source Copernicus software, which is based on Folding@home's MSM and other parallelizing methods and aims to improve the efficiency and scaling of molecular simulations on large computer clusters or supercomputers. Summaries of all scientific findings from Folding@home are posted on the Folding@home website after publication.

Alzheimer's disease

Alzheimer's disease is an incurable neurodegenerative disease which most often affects the elderly and accounts for more than half of all cases of dementia. Its exact cause remains unknown, but the disease is identified as a protein misfolding disease. Alzheimer's is associated with toxic aggregations of the amyloid beta (Aβ) peptide, caused by Aβ misfolding and clumping together with other Aβ peptides. These Aβ aggregates then grow into significantly larger senile plaques, a pathological marker of Alzheimer's disease. Due to the heterogeneous nature of these aggregates, experimental methods such as X-ray crystallography and nuclear magnetic resonance (NMR) have had difficulty characterizing their structures. Moreover, atomic simulations of Aβ aggregation are highly demanding computationally due to their size and complexity.

Preventing Aβ aggregation is a promising method to developing therapeutic drugs for Alzheimer's disease, according to Naeem and Fazili in a literature review article. In 2008, Folding@home simulated the dynamics of Aβ aggregation in atomic detail over timescales of the order of tens of seconds. Prior studies were only able to simulate about 10 microseconds. Folding@home was able to simulate Aβ folding for six orders of magnitude longer than formerly possible. Researchers used the results of this study to identify a beta hairpin that was a major source of molecular interactions within the structure. The study helped prepare the Pande lab for future aggregation studies and for further research to find a small peptide which may stabilize the aggregation process.

In December 2008, Folding@home found several small drug candidates which appear to inhibit the toxicity of Aβ aggregates. In 2010, in close cooperation with the Center for Protein Folding Machinery, these drug leads began to be tested on biological tissue. In 2011, Folding@home completed simulations of several mutations of Aβ that appear to stabilize the aggregate formation, which could aid in the development of therapeutic drug therapies for the disease and greatly assist with experimental nuclear magnetic resonance spectroscopy studies of Aβ oligomers. Later that year, Folding@home began simulations of various Aβ fragments to determine how various natural enzymes affect the structure and folding of Aβ.

Huntington's disease
Huntington's disease is a neurodegenerative genetic disorder that is associated with protein misfolding and aggregation. Excessive repeats of the glutamine amino acid at the N-terminus of the huntingtin protein cause aggregation, and although the behavior of the repeats is not completely understood, it does lead to the cognitive decline associated with the disease. As with other aggregates, there is difficulty in experimentally determining its structure. Scientists are using Folding@home to study the structure of the huntingtin protein aggregate and to predict how it forms, assisting with rational drug design methods to stop the aggregate formation. The N17 fragment of the huntingtin protein accelerates this aggregation, and while there have been several mechanisms proposed, its exact role in this process remains largely unknown. Folding@home has simulated this and other fragments to clarify their roles in the disease. Since 2008, its drug design methods for Alzheimer's disease have been applied to Huntington's.

Cancer
More than half of all known cancers involve mutations of p53, a tumor suppressor protein present in every cell which regulates the cell cycle and signals for cell death in the event of damage to DNA. Specific mutations in p53 can disrupt these functions, allowing an abnormal cell to continue growing unchecked, resulting in the development of tumors. Analysis of these mutations helps explain the root causes of p53-related cancers. In 2004, Folding@home was used to perform the first molecular dynamics study of the refolding of p53's protein dimer in an all-atom simulation of water. The simulation's results agreed with experimental observations and gave insights into the refolding of the dimer that were formerly unobtainable. This was the first peer reviewed publication on cancer from a distributed computing project. The following year, Folding@home powered a new method to identify the amino acids crucial for the stability of a given protein, which was then used to study mutations of p53. The method was reasonably successful in identifying cancer-promoting mutations and determined the effects of specific mutations which could not otherwise be measured experimentally.

Folding@home is also used to study protein chaperones, heat shock proteins which play essential roles in cell survival by assisting with the folding of other proteins in the crowded and chemically stressful environment within a cell. Rapidly growing cancer cells rely on specific chaperones, and some chaperones play key roles in chemotherapy resistance. Inhibitions to these specific chaperones are seen as potential modes of action for efficient chemotherapy drugs or for reducing the spread of cancer. Using Folding@home and working closely with the Center for Protein Folding Machinery, the Pande lab hopes to find a drug which inhibits those chaperones involved in cancerous cells. Researchers are also using Folding@home to study other molecules related to cancer, such as the enzyme Src kinase, and some forms of the engrailed homeodomain: a large protein which may be involved in many diseases, including cancer. In 2011, Folding@home began simulations of the dynamics of the small knottin protein EETI, which can identify carcinomas in imaging scans by binding to surface receptors of cancer cells.

Interleukin 2 (IL-2) is a protein that helps T cells of the immune system attack pathogens and tumors. However, its use as a cancer treatment is restricted due to serious side effects such as pulmonary edema. IL-2 binds to these pulmonary cells differently than it does to T cells, so IL-2 research involves understanding the differences between these binding mechanisms. In 2012, Folding@home assisted with the discovery of a mutant form of IL-2 which is three hundred times more effective in its immune system role but carries fewer side effects. In experiments, this altered form significantly outperformed natural IL-2 in impeding tumor growth. Pharmaceutical companies have expressed interest in the mutant molecule, and the National Institutes of Health are testing it against a large variety of tumor models to try to accelerate its development as a therapeutic.

Osteogenesis imperfecta
Osteogenesis imperfecta, known as brittle bone disease, is an incurable genetic bone disorder which can be lethal. Those with the disease are unable to make functional connective bone tissue. This is most commonly due to a mutation in Type-I collagen, which fulfills a variety of structural roles and is the most abundant protein in mammals. The mutation causes a deformation in collagen's triple helix structure, which if not naturally destroyed, leads to abnormal and weakened bone tissue. In 2005, Folding@home tested a new quantum mechanical method that improved upon prior simulation methods, and which may be useful for future computing studies of collagen. Although researchers have used Folding@home to study collagen folding and misfolding, the interest stands as a pilot project compared to Alzheimer's and Huntington's research.

Viruses
Folding@home is assisting in research towards preventing some viruses, such as influenza and HIV, from recognizing and entering biological cells. In 2011, Folding@home began simulations of the dynamics of the enzyme RNase H, a key component of HIV, to try to design drugs to deactivate it. Folding@home has also been used to study membrane fusion, an essential event for viral infection and a wide range of biological functions. This fusion involves conformational changes of viral fusion proteins and protein docking, but the exact molecular mechanisms behind fusion remain largely unknown. Fusion events may consist of over a half million atoms interacting for hundreds of microseconds. This complexity limits typical computer simulations to about ten thousand atoms over tens of nanoseconds: a difference of several orders of magnitude. The development of models to predict the mechanisms of membrane fusion will assist in the scientific understanding of how to target the process with antiviral drugs. In 2006, scientists applied Markov state models and the Folding@home network to discover two pathways for fusion and gain other mechanistic insights.

Following detailed simulations from Folding@home of small cells known as vesicles, in 2007, the Pande lab introduced a new computing method to measure the topology of its structural changes during fusion. In 2009, researchers used Folding@home to study mutations of influenza hemagglutinin, a protein that attaches a virus to its host cell and assists with viral entry. Mutations to hemagglutinin affect how well the protein binds to a host's cell surface receptor molecules, which determines how infective the virus strain is to the host organism. Knowledge of the effects of hemagglutinin mutations assists in the development of antiviral drugs. As of 2012, Folding@home continues to simulate the folding and interactions of hemagglutinin, complementing experimental studies at the University of Virginia.

In March 2020, Folding@home launched a program to assist researchers around the world who are working on finding a cure and learning more about the coronavirus pandemic. The initial wave of projects simulate potentially druggable protein targets from SARS-CoV-2 virus, and the related SARS-CoV virus, about which there is significantly more data available.

Drug design
Drugs function by binding to specific locations on target molecules and causing some desired change, such as disabling a target or causing a conformational change. Ideally, a drug should act very specifically, and bind only to its target without interfering with other biological functions. However, it is difficult to precisely determine where and how tightly two molecules will bind. Due to limits in computing power, current in silico methods usually must trade speed for accuracy; e.g., use rapid protein docking methods instead of computationally costly free energy calculations. Folding@home's computing performance allows researchers to use both methods, and evaluate their efficiency and reliability. Computer-assisted drug design has the potential to expedite and lower the costs of drug discovery. In 2010, Folding@home used MSMs and free energy calculations to predict the native state of the villin protein to within 1.8 angstrom (Å) root mean square deviation (RMSD) from the crystalline structure experimentally determined through X-ray crystallography. This accuracy has implications to future protein structure prediction methods, including for intrinsically unstructured proteins. Scientists have used Folding@home to research drug resistance by studying vancomycin, an antibiotic drug of last resort, and beta-lactamase, a protein that can break down antibiotics like penicillin.

Chemical activity occurs along a protein's active site. Traditional drug design methods involve tightly binding to this site and blocking its activity, under the assumption that the target protein exists in one rigid structure. However, this approach works for approximately only 15% of all proteins. Proteins contain allosteric sites which, when bound to by small molecules, can alter a protein's conformation and ultimately affect the protein's activity. These sites are attractive drug targets, but locating them is very computationally costly. In 2012, Folding@home and MSMs were used to identify allosteric sites in three medically relevant proteins: beta-lactamase, interleukin-2, and RNase H.

Approximately half of all known antibiotics interfere with the workings of a bacteria's ribosome, a large and complex biochemical machine that performs protein biosynthesis by translating messenger RNA into proteins. Macrolide antibiotics clog the ribosome's exit tunnel, preventing synthesis of essential bacterial proteins. In 2007, the Pande lab received a grant to study and design new antibiotics. In 2008, they used Folding@home to study the interior of this tunnel and how specific molecules may affect it. The full structure of the ribosome was determined only as of 2011, and Folding@home has also simulated ribosomal proteins, as many of their functions remain largely unknown.

Potential applications in biomedical research
There are many more protein misfolding promoted diseases that can be benefited from Folding@home to either discern the misfolded protein structure or the misfolding kinetics, and assist in drug design in the future. The often fatal prion diseases is among the most significant.

Prion diseases

A prion (PrP) is a transmembrane cellular protein found widely in eukaryotic cells. In mammals, it is more abundant in the central nervous system. Although its function is unknown, its high conservation among species indicates an important role in the cellular function. The conformational change from the normal prion protein (PrPc, stands for cellular) to the disease causing isoform PrPSc (stands for prototypical prion disease–scrapie) causes a host of diseases collectly known as transmissible spongiform encephalopathies (TSEs), including Bovine spongiform encephalopathy (BSE) in bovine, Creutzfeldt-Jakob disease (CJD) and fatal insomnia in human, chronic wasting disease (CWD) in the deer family. The conformational change is widely accepted as the result of protein misfolding. What distinguishes TSEs from other protein misfolding diseases is its transmissible nature. The 'seeding' of the infectious PrPSc, either arising spontaneously, hereditary or acquired via exposure to contaminated tissues, can cause a chain reaction of transforming normal PrPc into fibrils aggregates or amyloid like plaques consist of PrPSc.

The molecular structure of PrPSc has not been fully characterized due to its aggregated nature. Neither is known much about the mechanism of the protein misfolding nor its kinetics. Using the known structure of PrPc and the results of the in vitro and in vivo studies described below, Folding@home could be valuable in elucidating how PrPSc is formed and how the infectious protein arrange themselves to form fibrils and amyloid like plaques, bypassing the requirement to purify PrPSc or dissolve the aggregates.

The PrPc has been enzymatically dissociated from the membrane and purified, its structure studied using structure characterization techniques such as NMR spectroscopy and X-ray crystallography. Post-translational PrPc has 231 amino acids (aa) in murine. The molecule consists of a long and unstructured amino terminal region spanning up to aa residue 121 and a structured carboxy terminal domain. This globular domain harbors two short sheet-forming anti-parallel β-strands (aa 128 to 130 and aa 160 to 162 in murine PrPc) and three α-helices (helix I: aa 143 to 153; helix II: aa 171 to 192; helix III: aa 199 to 226 in murine PrPc), Helices II and III are anti-parallel orientated and connected by a short loop. Their structural stability is supported by a disulfide bridge, which is parallel to both sheet-forming β-strands. These α-helices and the β-sheet form the rigid core of the globular domain of PrPc.

The disease causing PrPSc is proteinase K resistant and insoluble. Attempts to purify it from the brains of infected animals invariably yield heterogeneous mixtures and aggregated states that are not amenable to characterization by NMR spectroscopy or X-ray crystallography. However, it is a general consensus that PrPSc contains a high percentage of tightly stacked β-sheets than the normal PrPc that renders the protein insoluble and resistant to proteinase. Using techniques of cryoelectron microscopy and structural modeling based on similar common protein structures, it has been discovered that PrPSc contains ß-sheets in the region of aa 81–95 to aa 171, while the carboxy terminal structure is supposedly preserved, retaining the disulfide-linked α-helical conformation in the normal PrPc. These ß-sheets form a parallel left-handed beta-helix. Three PrPSc molecules are believed to form a primary unit and therefore build the basis for the so-called scrapie-associated fibrils. The catalytic activity depends on the size of the particle. PrPSc particles which consist of only 14-28 PrPc molecules exhibit the highest rate of infectivity and conversion.

Despite the difficulty to purify and characterize PrPSc, from the known molecular structure of PrPc and using transgenic mice and N-terminal deletion, the potential 'hot spots' of protein misfolding leading to the pathogenic PrPSc could be deduced and Folding@home could be of great value in confirming these. Studies found that both the primary and secondary structure of the prion protein can be of significance of the conversion.

There are more than twenty mutations of the prion protein gene (PRNP) that are known to be associated with or that are directly linked to the hereditary form of human TSEs [56], indicating single amino acids at certain position, likely within the carboxy domain, of the PrPc can affect the susceptibility to TSEs.

The post-translational amino terminal region of PrPc consists of residues 23-120 which make up nearly half of the amino sequence of full-length matured PrPc. There are two sections in the amino terminal region that may influence conversion. First, residues 52-90 contains an octapeptide repeat (5 times) region that likely influences the initial binding (via the octapeptide repeats) and also the actual conversion via the second section of aa 108–124. The highly hydrophobic AGAAAAGA is located between aa residue 113 and 120 and is described as putative aggregation site, although this sequence requires its flanking parts to form fibrillar aggregates.

In the carboxy globular domain, among the three helices, study show that helix II has a significant higher propensity to β-strand conformation. Due to the high conformational flexvoribility seen between residues 114-125 (part of the unstructured N-terminus chain) and the high β-strand propensity of helix II, only moderate changes in the environmental conditions or interactions might be sufficient to induce misfolding of PrPc and subsequent fibril formation.

Other studies of NMR structures of PrPc showed that these residues (~108–189) contain most of the folded domain including both β-strands, the first two α-helices, and the loop/turn regions connecting them, but not the helix III. Small changes within the loop/turn structures of PrPc itself could be important in the conversion as well. In another study, Riek et al. showed that the two small regions of β-strand upstream of the loop regions act as a nucleation site for the conformational conversion of the loop/turn and α-helical structures in PrPc to β-sheet.

The energy threshold for the conversion are not necessarily high. The folding stability, i.e. the free energy of a globular protein in its environment is in the range of one or two hydrogen bonds thus allows the transition to an isoform without the requirement of high transition energy.

From the respective of the interactions among the PrPc molecules, hydrophobic interactions play a crucial role in the formation of β-sheets, a hallmark of PrPSc, as the sheets bring fragments of polypeptide chains into close proximity. Indeed, Kutznetsov and Rackovsky  showed that disease-promoting mutations in the human PrPc had a statistically significant tendency towards increasing local hydrophobicity.

In vitro experiments showed the kinetics of misfolding has an initial lag phase followed by a rapid growth phase of fibril formation. It is likely that PrPc goes through some intermediate states, such as at least partially unfolded or degraded, before finally ending up as part of an amyloid fibril.

Patterns of participation
Like other distributed computing projects, Folding@home is an online citizen science project. In these projects non-specialists contribute computer processing power or help to analyze data produced by professional scientists. Participants receive little or no obvious reward.

Research has been carried out into the motivations of citizen scientists and most of these studies have found that participants are motivated to take part because of altruistic reasons; that is, they want to help scientists and make a contribution to the advancement of their research. Many participants in citizen science have an underlying interest in the topic of the research and gravitate towards projects that are in disciplines of interest to them. Folding@home is no different in that respect. Research carried out recently on over 400 active participants revealed that they wanted to help make a contribution to research and that many had friends or relatives affected by the diseases that the Folding@home scientists investigate.

Folding@home attracts participants who are computer hardware enthusiasts. These groups bring considerable expertise to the project and are able to build computers with advanced processing power. Other distributed computing projects attract these types of participants and projects are often used to benchmark the performance of modified computers, and this aspect of the hobby is accommodated through the competitive nature of the project. Individuals and teams can compete to see who can process the most computer processing units (CPUs).

This latest research on Folding@home involving interview and ethnographic observation of online groups showed that teams of hardware enthusiasts can sometimes work together, sharing best practice with regard to maximizing processing output. Such teams can become communities of practice, with a shared language and online culture. This pattern of participation has been observed in other distributed computing projects.

Another key observation of Folding@home participants is that many are male. This has also been observed in other distributed projects. Furthermore, many participants work in computer and technology-based jobs and careers.

Not all Folding@home participants are hardware enthusiasts. Many participants run the project software on unmodified machines and do take part competitively. By January 2020, the number of users was down to 30,000. However, it is difficult to ascertain what proportion of participants are hardware enthusiasts. Although, according to the project managers, the contribution of the enthusiast community is substantially larger in terms of processing power.

Performance

Supercomputer FLOPS performance is assessed by running the legacy LINPACK benchmark. This short-term testing has difficulty in accurately reflecting sustained performance on real-world tasks because LINPACK more efficiently maps to supercomputer hardware. Computing systems vary in architecture and design, so direct comparison is difficult. Despite this, FLOPS remain the primary speed metric used in supercomputing. In contrast, Folding@home determines its FLOPS using wall-clock time by measuring how much time its work units take to complete.

On September 16, 2007, due in large part to the participation of PlayStation 3 consoles, the Folding@home project officially attained a sustained performance level higher than one native petaFLOPS, becoming the first computing system of any kind to do so. Top500's fastest supercomputer at the time was BlueGene/L, at 0.280 petaFLOPS. The following year, on May 7, 2008, the project attained a sustained performance level higher than two native petaFLOPS, followed by the three and four native petaFLOPS milestones in August 2008 and September 28, 2008 respectively. On February 18, 2009, Folding@home achieved five native petaFLOPS, and was the first computing project to meet these five levels. In comparison, November 2008's fastest supercomputer was IBM's Roadrunner at 1.105 petaFLOPS. On November 10, 2011, Folding@home's performance exceeded six native petaFLOPS with the equivalent of nearly eight x86 petaFLOPS. In mid-May 2013, Folding@home attained over seven native petaFLOPS, with the equivalent of 14.87 x86 petaFLOPS. It then reached eight native petaFLOPS on June 21, followed by nine on September 9 of that year, with 17.9 x86 petaFLOPS. On May 11, 2016 Folding@home announced that it was moving towards reaching the 100 x86 petaFLOPS mark.

Further use grew from increased awareness and participation in the project from the coronavirus pandemic in 2020. On March 20, 2020 Folding@home announced via Twitter that it was running with over 470 native petaFLOPS, the equivalent of 958 x86 petaFLOPS. By March 25 it reached 768 petaFLOPS, or 1.5 x86 exaFLOPS, making it the first exaFLOP computing system.

, the computing power of Folding@home stands at 31 petaFLOPS, or 64 x86 petaFLOPS.

Points
Similarly to other distributed computing projects, Folding@home quantitatively assesses user computing contributions to the project through a credit system. All units from a given protein project have uniform base credit, which is determined by benchmarking one or more work units from that project on an official reference machine before the project is released. Each user receives these base points for completing every work unit, though through the use of a passkey they can receive added bonus points for reliably and rapidly completing units which are more demanding computationally or have a greater scientific priority. Users may also receive credit for their work by clients on multiple machines. This point system attempts to align awarded credit with the value of the scientific results.

Users can register their contributions under a team, which combine the points of all their members. A user can start their own team, or they can join an existing team. In some cases, a team may have their own community-driven sources of help or recruitment such as an Internet forum. The points can foster friendly competition between individuals and teams to compute the most for the project, which can benefit the folding community and accelerate scientific research. Individual and team statistics are posted on the Folding@home website.

If a user does not form a new team, or does not join an existing team, that user automatically becomes part of a "Default" team. This "Default" team has a team number of "0". Statistics are accumulated for this "Default" team as well as for specially named teams.

Software
Folding@home software at the user's end involves three primary components: work units, cores, and a client.

Work units
A work unit is the protein data that the client is asked to process. Work units are a fraction of the simulation between the states in a Markov model. After the work unit has been downloaded and completely processed by a volunteer's computer, it is returned to Folding@home servers, which then award the volunteer the credit points. This cycle repeats automatically. All work units have associated deadlines, and if this deadline is exceeded, the user may not get credit and the unit will be automatically reissued to another participant. As protein folding occurs serially, and many work units are generated from their predecessors, this allows the overall simulation process to proceed normally if a work unit is not returned after a reasonable period of time. Due to these deadlines, the minimum system requirement for Folding@home is a Pentium 3 450 MHz CPU with Streaming SIMD Extensions (SSE). However, work units for high-performance clients have a much shorter deadline than those for the uniprocessor client, as a major part of the scientific benefit is dependent on rapidly completing simulations.

Before public release, work units go through several quality assurance steps to keep problematic ones from becoming fully available. These testing stages include internal, beta, and advanced, before a final full release across Folding@home. Folding@home's work units are normally processed only once, except in the rare event that errors occur during processing. If this occurs for three different users, the unit is automatically pulled from distribution. The Folding@home support forum can be used to differentiate between issues arising from problematic hardware and bad work units.

Cores

Specialized molecular dynamics programs, referred to as "FahCores" and often abbreviated "cores", perform the calculations on the work unit as a background process. A large majority of Folding@home's cores are based on GROMACS, one of the fastest and most popular molecular dynamics software packages, which largely consists of manually optimized assembly language code and hardware optimizations. Although GROMACS is open-source software and there is a cooperative effort between the Pande lab and GROMACS developers, Folding@home uses a closed-source license to help ensure data validity. Less active cores include ProtoMol and SHARPEN. Folding@home has used AMBER, CPMD, Desmond, and TINKER, but these have since been retired and are no longer in active service. Some of these cores perform explicit solvation calculations in which the surrounding solvent (usually water) is modeled atom-by-atom; while others perform implicit solvation methods, where the solvent is treated as a mathematical continuum. The core is separate from the client to enable the scientific methods to be updated automatically without requiring a client update. The cores periodically create calculation checkpoints so that if they are interrupted they can resume work from that point upon startup.

Client

A Folding@home participant installs a client program on their personal computer. The user interacts with the client, which manages the other software components in the background. Through the client, the user may pause the folding process, open an event log, check the work progress, or view personal statistics. The computer clients run continuously in the background at a very low priority, using idle processing power so that normal computer use is unaffected. The maximum CPU use can be adjusted via client settings. The client connects to a Folding@home server and retrieves a work unit and may also download the appropriate core for the client's settings, operating system, and the underlying hardware architecture. After processing, the work unit is returned to the Folding@home servers. Computer clients are tailored to uniprocessor and multi-core processor systems, and graphics processing units. The diversity and power of each hardware architecture provides Folding@home with the ability to efficiently complete many types of simulations in a timely manner (in a few weeks or months rather than years), which is of significant scientific value. Together, these clients allow researchers to study biomedical questions formerly considered impractical to tackle computationally.

Professional software developers are responsible for most of Folding@home's code, both for the client and server-side. The development team includes programmers from Nvidia, ATI, Sony, and Cauldron Development. Clients can be downloaded only from the official Folding@home website or its commercial partners, and will only interact with Folding@home computer files. They will upload and download data with Folding@home's data servers (over port 8080, with 80 as an alternate), and the communication is verified using 2048-bit digital signatures. While the client's graphical user interface (GUI) is open-source, the client is proprietary software citing security and scientific integrity as the reasons.

However, this rationale of using proprietary software is disputed since while the license could be enforceable in the legal domain retrospectively, it does not practically prevent the modification (also known as patching) of the executable binary files. Likewise, binary-only distribution does not prevent the malicious modification of executable binary-code, either through a man-in-the-middle attack while being downloaded via the internet, or by the redistribution of binaries by a third-party that have been previously modified either in their binary state (i.e. patched), or by decompiling and recompiling them after modification. These modifications are possible unless the binary files – and the transport channel – are signed and the recipient person/system is able to verify the digital signature, in which case unwarranted modifications should be detectable, but not always. Either way, since in the case of Folding@home the input data and output result processed by the client-software are both digitally signed, the integrity of work can be verified independently from the integrity of the client software itself.

Folding@home uses the Cosm software libraries for networking. Folding@home was launched on October 1, 2000, and was the first distributed computing project aimed at bio-molecular systems. Its first client was a screensaver, which would run while the computer was not otherwise in use. In 2004, the Pande lab collaborated with David P. Anderson to test a supplemental client on the open-source BOINC framework. This client was released to closed beta in April 2005; however, the method became unworkable and was shelved in June 2006.

Graphics processing units
The specialized hardware of graphics processing units (GPU) is designed to accelerate rendering of 3-D graphics applications such as video games and can significantly outperform CPUs for some types of calculations. GPUs are one of the most powerful and rapidly growing computing platforms, and many scientists and researchers are pursuing general-purpose computing on graphics processing units (GPGPU). However, GPU hardware is difficult to use for non-graphics tasks and usually requires significant algorithm restructuring and an advanced understanding of the underlying architecture. Such customization is challenging, more so to researchers with limited software development resources. Folding@home uses the open-source OpenMM library, which uses a bridge design pattern with two application programming interface (API) levels to interface molecular simulation software to an underlying hardware architecture. With the addition of hardware optimizations, OpenMM-based GPU simulations need no significant modification but achieve performance nearly equal to hand-tuned GPU code, and greatly outperform CPU implementations.

Before 2010, the computing reliability of GPGPU consumer-grade hardware was largely unknown, and circumstantial evidence related to the lack of built-in error detection and correction in GPU memory raised reliability concerns. In the first large-scale test of GPU scientific accuracy, a 2010 study of over 20,000 hosts on the Folding@home network detected soft errors in the memory subsystems of two-thirds of the tested GPUs. These errors strongly correlated to board architecture, though the study concluded that reliable GPU computing was very feasible as long as attention is paid to the hardware traits, such as software-side error detection.

The first generation of Folding@home's GPU client (GPU1) was released to the public on October 2, 2006, delivering a 20–30 times speedup for some calculations over its CPU-based GROMACS counterparts. It was the first time GPUs had been used for either distributed computing or major molecular dynamics calculations. GPU1 gave researchers significant knowledge and experience with the development of GPGPU software, but in response to scientific inaccuracies with DirectX, on April 10, 2008, it was succeeded by GPU2, the second generation of the client. Following the introduction of GPU2, GPU1 was officially retired on June 6. Compared to GPU1, GPU2 was more scientifically reliable and productive, ran on ATI and CUDA-enabled Nvidia GPUs, and supported more advanced algorithms, larger proteins, and real-time visualization of the protein simulation. Following this, the third generation of Folding@home's GPU client (GPU3) was released on May 25, 2010. While backward compatible with GPU2, GPU3 was more stable, efficient, and flexibile in its scientific abilities, and used OpenMM on top of an OpenCL framework. Although these GPU3 clients did not natively support the operating systems Linux and macOS, Linux users with Nvidia graphics cards were able to run them through the Wine software application. GPUs remain Folding@home's most powerful platform in FLOPS. As of November 2012, GPU clients account for 87% of the entire project's x86 FLOPS throughput.

Native support for Nvidia and AMD graphics cards under Linux was introduced with FahCore 17, which uses OpenCL rather than CUDA.

PlayStation 3

From March 2007 until November 2012, Folding@home took advantage of the computing power of PlayStation 3s. At the time of its inception, its main streaming Cell processor delivered a 20 times speed increase over PCs for some calculations, processing power which could not be found on other systems such as the Xbox 360. The PS3's high speed and efficiency introduced other opportunities for worthwhile optimizations according to Amdahl's law, and significantly changed the tradeoff between computing efficiency and overall accuracy, allowing the use of more complex molecular models at little added computing cost. This allowed Folding@home to run biomedical calculations that would have been otherwise infeasible computationally.

The PS3 client was developed in a collaborative effort between Sony and the Pande lab and was first released as a standalone client on March 23, 2007. Its release made Folding@home the first distributed computing project to use PS3s. On September 18 of the following year, the PS3 client became a channel of Life with PlayStation on its launch. In the types of calculations it can perform, at the time of its introduction, the client fit in between a CPU's flexibility and a GPU's speed. However, unlike clients running on personal computers, users were unable to perform other activities on their PS3 while running Folding@home. The PS3's uniform console environment made technical support easier and made Folding@home more user friendly. The PS3 also had the ability to stream data quickly to its GPU, which was used for real-time atomic-level visualizing of the current protein dynamics.

On November 6, 2012, Sony ended support for the Folding@home PS3 client and other services available under Life with PlayStation. Over its lifetime of five years and seven months, more than 15 million users contributed over 100 million hours of computing to Folding@home, greatly assisting the project with disease research. Following discussions with the Pande lab, Sony decided to terminate the application. Pande considered the PlayStation 3 client a "game changer" for the project.

Multi-core processing client
Folding@home can use the parallel computing abilities of modern multi-core processors. The ability to use several CPU cores simultaneously allows completing the full simulation far faster. Working together, these CPU cores complete single work units proportionately faster than the standard uniprocessor client. This method is scientifically valuable because it enables much longer simulation trajectories to be performed in the same amount of time, and reduces the traditional difficulties of scaling a large simulation to many separate processors. A 2007 publication in the Journal of Molecular Biology relied on multi-core processing to simulate the folding of part of the villin protein approximately 10 times longer than was possible with a single-processor client, in agreement with experimental folding rates.

In November 2006, first-generation symmetric multiprocessing (SMP) clients were publicly released for open beta testing, referred to as SMP1. These clients used Message Passing Interface (MPI) communication protocols for parallel processing, as at that time the GROMACS cores were not designed to be used with multiple threads. This was the first time a distributed computing project had used MPI. Although the clients performed well in Unix-based operating systems such as Linux and macOS, they were troublesome under Windows. On January 24, 2010, SMP2, the second generation of the SMP clients and the successor to SMP1, was released as an open beta and replaced the complex MPI with a more reliable thread-based implementation.

SMP2 supports a trial of a special category of bigadv work units, designed to simulate proteins that are unusually large and computationally intensive and have a great scientific priority. These units originally required a minimum of eight CPU cores, which was raised to sixteen later, on February 7, 2012. Along with these added hardware requirements over standard SMP2 work units, they require more system resources such as random-access memory (RAM) and Internet bandwidth. In return, users who run these are rewarded with a 20% increase over SMP2's bonus point system. The bigadv category allows Folding@home to run especially demanding simulations for long times that had formerly required use of supercomputing clusters and could not be performed anywhere else on Folding@home. Many users with hardware able to run bigadv units have later had their hardware setup deemed ineligible for bigadv work units when CPU core minimums were increased, leaving them only able to run the normal SMP work units. This frustrated many users who invested significant amounts of money into the program only to have their hardware be obsolete for bigadv purposes shortly after. As a result, Pande announced in January 2014 that the bigadv program would end on January 31, 2015.

V7

The V7 client is the seventh and latest generation of the Folding@home client software, and is a full rewrite and unification of the prior clients for Windows, macOS, and Linux operating systems. It was released on March 22, 2012. Like its predecessors, V7 can run Folding@home in the background at a very low priority, allowing other applications to use CPU resources as they need. It is designed to make the installation, start-up, and operation more user-friendly for novices, and offer greater scientific flexibility to researchers than prior clients. V7 uses Trac for managing its bug tickets so that users can see its development process and provide feedback.

V7 consists of four integrated elements. The user typically interacts with V7's open-source GUI, named FAHControl. This has Novice, Advanced, and Expert user interface modes, and has the ability to monitor, configure, and control many remote folding clients from one computer. FAHControl directs FAHClient, a back-end application that in turn manages each FAHSlot (or slot). Each slot acts as replacement for the formerly distinct Folding@home v6 uniprocessor, SMP, or GPU computer clients, as it can download, process, and upload work units independently. The FAHViewer function, modeled after the PS3's viewer, displays a real-time 3-D rendering, if available, of the protein currently being processed.

Google Chrome
In 2014, a client for the Google Chrome and Chromium web browsers was released, allowing users to run Folding@home in their web browser. The client used Google's Native Client (NaCl) feature on Chromium-based web browsers to run the Folding@home code at near-native speed in a sandbox on the user's machine. Due to the phasing out of NaCL and changes at Folding@home, the web client was permanently shut down in June 2019.

Android
In July 2015, a client for Android mobile phones was released on Google Play for devices running Android 4.4 KitKat or newer.

On February 16, 2018, the Android client, which was offered in cooperation with Sony, was removed from Google Play. Plans were announced to offer an open source alternative in the future.

Comparison to other molecular simulators
Rosetta@home is a distributed computing project aimed at protein structure prediction and is one of the most accurate tertiary structure predictors. The conformational states from Rosetta's software can be used to initialize a Markov state model as starting points for Folding@home simulations. Conversely, structure prediction algorithms can be improved from thermodynamic and kinetic models and the sampling aspects of protein folding simulations. As Rosetta only tries to predict the final folded state, and not how folding proceeds, Rosetta@home and Folding@home are complementary and address very different molecular questions.

Anton is a special-purpose supercomputer built for molecular dynamics simulations. In October 2011, Anton and Folding@home were the two most powerful molecular dynamics systems. Anton is unique in its ability to produce single ultra-long computationally costly molecular trajectories, such as one in 2010 which reached the millisecond range. These long trajectories may be especially helpful for some types of biochemical problems. However, Anton does not use Markov state models (MSM) for analysis. In 2011, the Pande lab constructed a MSM from two 100-µs Anton simulations and found alternative folding pathways that were not visible through Anton's traditional analysis. They concluded that there was little difference between MSMs constructed from a limited number of long trajectories or one assembled from many shorter trajectories. In June 2011 Folding@home added sampling of an Anton simulation in an effort to better determine how its methods compare to Anton's. However, unlike Folding@home's shorter trajectories, which are more amenable to distributed computing and other parallelizing methods, longer trajectories do not require adaptive sampling to sufficiently sample the protein's phase space. Due to this, it is possible that a combination of Anton's and Folding@home's simulation methods would provide a more thorough sampling of this space.

See also

 BOINC
 DreamLab, for use on smartphones
 Foldit
 List of distributed computing projects
 Comparison of software for molecular mechanics modeling
 Molecular modeling on GPUs
 SETI@home
 Storage@home
 Molecule editor
 Volunteer computing
 World Community Grid

References

Sources

External links

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