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This interaction inhibits muscle contractions, giving the appearance of smooth muscle.
A number of computational tools have been developed for the prediction of the location of binding sites on proteins.
These can be broadly classified into sequence based or structure based.
Sequence based methods rely on the assumption that the sequences of functionally conserved portions of proteins such as binding site are conserved.
Structure based methods require the 3D structure of the protein.
These methods in turn can be subdivided into template and pocket based methods.
Template based methods search for 3D similarities between the target protein and proteins with known binding sites.
The pocket based methods search for concave surfaces or buried pockets in the target protein that possess features such as hydrophobicity and hydrogen bonding capacity that would allow them to bind ligands with high affinity.
Even though the term pocket is used here, similar methods can be used to predict binding sites used in protein-protein interactions that are usually more planar, not in pockets.
Sabriel
Sabriel is a fantasy novel by Garth Nix, first published in 1995.
It is the first in his Old Kingdom series, followed by "Lirael", "Abhorsen", and "Goldenhand".
The novel is set in two neighbouring fictional countries: To the South lies Ancelstierre, which has a technology level and society similar to that of early-20th century Australia, and to the North lies the Old Kingdom, where both Free magic and Charter Magic exist — a fact officially denied by the government of Ancelstierre and disbelieved by most of Ancelstierre's inhabitants.
A wall separates the two countries.
Near the border some magic crosses the Wall, especially on days when the wind is blowing out of the Old Kingdom.
Since the fall of the Royal Family, dangerous entities roam, ranging from the undead to powerful sorcerers and Free Magic elementals.
These living Dead are raised by Necromancers, diviners of the dead who roam the Old Kingdom or live in Death, using Hands to do their bidding.
To remedy the problem of dangerous living dead, a necromancer under the title of Abhorsen uses a bandolier of Bells and a sword to put the dead to rest.
At the time of Sabriel, it is her father Terciel who has the job of putting the dead to rest in the Old Kingdom, especially difficult since a new evil is rising.
When the current Abhorsen is overcome by one such evil and beyond the Seventh Gate, he sends his bells (the primary tools of a necromancer and used in various ways to control the Dead) and sword to his daughter Sabriel via an undead messenger bound and under his control.
Sabriel is at an Ancelstierre school for girls to remain out of reach of those who might try to strike at her father through her and end the Abhorsen bloodline.
The bound undead is also attempting to speak, but she must enter death in order to make out the words.
She is instructed by her father (speaking through the undead messenger in Death) to return to the Old Kingdom to take on the role of Abhorsen and stop Kerrigor's return to Life.
While in Death obtaining her father's guidance, she narrowly avoids a fatal altercation with a Lesser Dead.
The book opens with Sabriel raising a freshly killed rabbit from death.
She is a young girl attending Wyverly College, an all-female boarding school in Ancelstierre.
An undead creature enters the dormitory where Sabriel lives and frightens all of the girls.
Sabriel, however, notices it is holding a satchel and is attempting to speak.
She enters Death to see what it is and notices strings attached to it passing over the waterfall of the First Gate; a sign that the creature is under the control of a necromancer further in Death.
It is very weak, but Sabriel makes out that it is a messenger bound by her father who is past the Seventh Gate of Death.
She is instructed by her father (through the messenger) that she is to take on the role of Abhorsen and defeat Kerrigor (a powerful Free Magic necromancer) who is attempting to make his way back into Life to break the Charter which binds the Free Magic and thus destroy the Charter of the Old Kingdom.
She retrieves the satchel which contains the Abhorsen's bandelier of bells, the Abhorsen's sword and a map of the Old Kingdom.
Having left her school, Sabriel crosses the Wall using papers given to her by her father.
Her destination is Abhorsen's House, the home of her father.
Near the wall, she meets a southern colonel and his troops.
The soldiers are using brute force to stop hordes of Shadow Hands from dismantling the Wall and crossing over.
The areas near the Wall are being evacuated and only those who are inhabitants of the Old Kingdom are allowed the cross.
As she continues her journey, Sabriel becomes aware that she is being stalked by a Mordicant, a powerful Dead creature.
She is able to outrun the creature and reach the safety of Abhorsen's House, which is located on an island in the center of the river.
(The Dead cannot cross fast and deep running water.)
Inside Abhorsen's house, Sabriel is able to rest and obtain food and other supplies, as well as armor.
She also meets Mogget, a Free Magic construct who takes the form of a small white cat, wearing a collar with a powerful binding spell on it and a miniature Saraneth hanging from it.
Mogget insists on accompanying her on her journey to find her father.
Later, they look out over the walls surrounding the house and discover the Dead attempting to build a bridge.
Sabriel performs a ritual to summon a flood of water and then flees the house by Paperwing (a magically propelled plane-like structure.)
While in the air, Sabriel and Mogget are attacked by the Dead, and Sabriel loosens Mogget's collar to avoid a fatal crash.
They fall into a sinkhole, where Mogget, in his unbound form, attempts to murder Sabriel.
However, she is able to bind him anew with a ring given to her for that purpose.
The next day, Sabriel and Mogget walk through a tunnel to another sinkhole, which Mogget determines to be Holehallow, the historical burial place of the royal family.
Each king is buried in a boat.
Sabriel discovers that the figurehead on one of the boats is not a wooden carving but an actual man, who has been imprisoned in that form for two hundred years.
The man tells Sabriel that he was a Royal Guard before his imprisonment, and asks to be called Touchstone (a jester's name) for reasons that remain cryptic.
Sabriel, Touchstone, and Mogget continue their journey, stopping to help rid a seaside village of a Dead creature.
They obtain a boat there and sail up the coast of the Old Kingdom until they reach Belisaere, the capital.
They find the Abhorsen in an underground reservoir in Belisaere, trapped in Death.
Since he has stayed too long in Death, he cannot return for long, but with what little time he has left, the Abhorsen tells Sabriel about the evil known as Kerrigor.
Kerrigor has risen far from Death and intends to wreak havoc in the Old Kingdom and Ancelstierre.
Sabriel releases her father from Death, and once they emerge from Death, father and daughter part for the last time — he, to ring the bell Astarael (the sound of which throws everyone who hears it far into the realm of Death) and delay Kerrigor's havoc; and she, to save Touchstone by bringing him (and herself) as far away from Astarael's music as possible.
To prevent him from losing to Death, she kisses him roughly in order to keep him focused on Life.
In the process of ringing Astarael, Sabriel's father releases Mogget.
They succeed, but as long as Kerrigor's body is intact, he will rise from Death again and again.
Sabriel and Touchstone use another Paperwing to bring them as close to the Wall as possible, and cross over to Ancelstierre to find Kerrigor's body, following the clairvoyant guidance of the Clayr twins Sanar and Ryelle.
They find the body, and Sabriel finally defeats Kerrigor by binding him with Ranna and Mogget's collar.
She dies but the previous Abhorsens prevent her from crossing into Final Death as she cannot die without someone else to take her place as Abhorsen.
She wakes up with Touchstone before her, and both Mogget and Kerrigor asleep, bound by Ranna (the first of seven necromantic bells that instills sleep and quiescence in those who hear it).
Thousands of years ago, seven of the Nine Bright Shiners sacrificed their powers to create the Charter: a combination of powerful objects (the Great Stones and the Wall) and three magic blood lines, known as the Abhorsen, the Clayr and the Royal Family.
Five of the Seven completely lost themselves (one in each object or blood line) while two remained somewhat independent.
One invested his/her power in the Royal bloodline, one in the Abhorsen's and one in the Clayr's (which is why the Clayr greet Sabriel as "cousin").
The remaining two, known as the "Wallmakers" invested themselves in several objects of power, including the Stones and Wall, then disappeared.
These artifacts, the Charter Stones, are sources of the web of Charter magic that maintains peace and order over the kingdom.
The Bloodlines all have a higher concentration of strong Charter mages than the general populace.
One of the most respected figures in the Old Kingdom, the Abhorsen uses both the dangerous Free Magic-based powers of a necromancer and the benevolent magic of the Charter to keep the gates of Death against the return of Dead spirits back into Life.
Sabriel and her father are members of the Abhorsen family.
They use the bells, named after the seven bright shiners that established the old kingdom, in tandem with their natural affinity with Death, granted by their ancestor bright shiner, to amplify their powers.
The bells, smallest to largest, are Ranna, Mosrael, Kibeth, Dyrim, Belgaer, Saraneth, and Astarael.
Saraneth, the "binder", is thought to be the original Abhorsen, and the bright shiner who invested her powers in this bloodline.
Her gift is "binding", just as the Abhorsens job is to "bind" the dead to Death.
Ranna the "sleepbringer", causing listeners to fall asleep; she is the least tricksome.
Mosrael, "the waker", wakes the dead, bringing them into life as it throws the necromancer farther into death.
Kibeth, "walker", forces the dead to march back into death, or wherever the ringer desires, although if the ringer is not careful it may end up "walking" her.
Dyrim is the "speaker", granting the ability of speech to the dead, or taking it away.
Belgaer is the "thinker" and can restore independent thought to the dead and resurrect old memories, but can also erase them in a careless hand.
Astarael is the "Sorrowful".
Last and final of the bells, she sends all who hear her, including the ringer, deep into death.
It is nearly impossible to return after hearing Astarael.
Like all three bloodlines, the Abhorsen bloodline not only defines their job (the Abhorsen may only be chosen from direct blood relatives) and grants them their powers, but also determines their appearance.
All members of the Abhorsen family have black hair and their skin is unnaturally pale.
Among the families guarding the Old Kingdom from disaster, and the only family guarding it from disasters from Death, Abhorsens are unique in their ability to sense Death.
They are able to identify undead creatures and differentiate them from the living, and cross over into Death to fight undead minions there and banish them to a final death.
They are also the only ones who have the proper authority to enter Death, and therefore the only Necromancers who retain uncorrupted charter marks and mage powers.
Their symbol is a silver key on a background of blue.
For centuries, the royalty justly ruled the Old Kingdom from their palace at the capital Belisaere as powerful upholders of the peace, until their fall by the hands of Kerrigor, or Prince Rogirek nicknamed Rogir, a rogue member of the royal family who killed his sisters and mother to use their blood to break the Great Charter Stones.
The Kingdom now suffers from their 200-year absence.
Unlike the Abhorsens, the Royalty cannot cross into Death at will and do not usually use Free Magic.
Their specialty lies in diplomacy and Charter magic.
They are connected to the Clayr and Abhorsens in that they're a Great Charter.
It is thought they are descended from Dyrim, the "speaker", because of their skill in diplomacy.
Their symbol is a golden tower on a sea of red.
The largest family among the magical bloodlines, the Clayr are arbiters of justice and foresight who see all from their glacier in the northernmost parts of the Old Kingdom.
The Clayr are a family of seers who may, when there is need, pool their powers together to see clear visions of the future, while individually they see only splinters.