Editing Protein tertiary structure (section)

== Determinants ==
{{Main article|Protein folding}}

=== Stability of native states ===

==== Thermostability ====
{{See also|Equilibrium unfolding}}
A protein folded into its [[native state]] or [[chemical conformation|native conformation]] typically has a lower [[Gibbs free energy]] (a combination of [[enthalpy]] and [[entropy]]) than the unfolded conformation. A protein will tend towards low-energy conformations, which will determine the protein's fold in the [[cell (biology)|cellular]] environment. Because many similar conformations will have similar energies, protein structures are [[Protein dynamics|dynamic]], fluctuating between these similar structures.

[[Globular protein]]s have a core of [[hydrophobic]] amino acid residues and a surface region of [[water]]-exposed, charged, [[hydrophilic]] residues. This arrangement may stabilize interactions within the tertiary structure. For example, in [[secrete]]d proteins, which are not bathed in [[cytoplasm]], [[disulfide bond]]s between [[cysteine]] residues help to maintain the tertiary structure. There is a commonality of stable tertiary structures seen in proteins of diverse function and diverse [[molecular evolution|evolution]]. For example, the [[TIM barrel]], named for the enzyme [[triosephosphateisomerase]], is a common tertiary structure as is the highly stable, [[dimer (chemistry)|dimeric]], [[coiled coil]] structure. Hence, proteins may be  classified by the structures they hold. Databases of proteins which use such a classification include ''[[Structural Classification of Proteins|SCOP]]'' and ''[[CATH]]''.

==== Kinetic traps ====
Folding [[Chemical kinetics|kinetics]] may trap a protein in a high-[[energy]] conformation, i.e. a high-energy intermediate conformation blocks access to the lowest-energy conformation. The high-energy conformation may contribute to the function of the protein. For example, the [[influenza]] [[hemagglutinin]] protein is a single polypeptide chain which when activated, is [[proteolysis|proteolytically]] cleaved to form two polypeptide chains. The two chains are held in a high-energy conformation. When the local [[pH]] drops, the protein undergoes an energetically favorable conformational rearrangement that enables it to penetrate the host [[cell membrane]].

==== Metastability ====
Some tertiary protein structures may exist in long-lived states that are not the expected most stable state. For example, many [[serpins]] (serine protease inhibitors) show this [[metastability]]. They undergo a [[conformational change]] when a loop of the protein is cut by a [[protease]].<ref name="whis">{{cite journal | author = Whisstock J | year = 2006 | title = Molecular gymnastics: serpiginous structure, folding and scaffolding | journal = Current Opinion in Structural Biology | volume = 16 | issue = 6| pages = 761–68 | pmid = 17079131 | doi=10.1016/j.sbi.2006.10.005}}</ref><ref>{{cite journal |author=Gettins PG |title=Serpin structure, mechanism, and function |journal=Chem Rev |volume=102 |issue=12 |pages=4751–804 |year=2002 |pmid=12475206 |doi=10.1021/cr010170 }}</ref><ref>{{cite journal |vauthors=Whisstock JC, Skinner R, Carrell RW, Lesk AM |title=Conformational changes in serpins: I. The native and cleaved conformations of alpha(1)-anti-trypsin |pmid=10669617|journal=J Mol Biol |year=2000 |volume=296  |pages=685–99 |doi=10.1006/jmbi.1999.3520 |issue=2}}</ref>

=== Chaperone proteins ===
It is commonly assumed that the native state of a protein is also the most [[thermodynamics|thermodynamically]] stable and that a protein will reach its native state, given its [[chemical kinetics]], before it is [[translation (genetics)|translated]]. Protein [[chaperone (protein)|chaperones]] within the cytoplasm of a cell assist a newly synthesised polypeptide to attain its native state. Some chaperone proteins are highly specific in their function, for example, [[protein disulfide isomerase]]; others are general in their function and may assist most globular proteins, for example, the [[prokaryotic]] [[GroEL]]/[[GroES]] system of proteins and the [[homology (biology)|homologous]] [[eukaryotic]] [[heat shock protein]]s (the Hsp60/Hsp10 system).

=== Cytoplasmic environment ===
Prediction of protein tertiary structure relies on knowing the protein's [[primary structure]] and comparing the possible predicted tertiary structure with known tertiary structures in [[protein data bank]]s. This only takes into account the cytoplasmic environment present at the time of [[protein biosynthesis|protein synthesis]] to the extent that a similar cytoplasmic environment may also have influenced the structure of the proteins recorded in the protein data bank.

=== Ligand binding ===
The structure of a protein, such as an [[enzyme]], may change upon binding of its natural ligands, for example a [[Cofactor (biochemistry)|cofactor]]. In this case, the structure of the protein bound to the ligand is known as holo structure,  while the unbound protein has an apo structure.<ref>{{cite journal|pmid=20066034|pmc=2796265|year=2010|last1=Seeliger|first1=D|title=Conformational transitions upon ligand binding: Holo-structure prediction from apo conformations|journal=PLOS Computational Biology|volume=6|issue=1|page=e1000634|last2=De Groot|first2=B. L.|doi=10.1371/journal.pcbi.1000634|bibcode=2010PLSCB...6E0634S |doi-access=free }}</ref>

Structure stabilized by the formation of weak bonds between amino acid side chains
- Determined by the folding of the polypeptide chain on itself (nonpolar residues are located
inside the protein, while polar residues are mainly located outside)
- Envelopment of the protein brings the protein closer and relates a-to located in distant regions of the sequence
- Acquisition of the tertiary structure leads to the formation of pockets and sites suitable for the recognition and
the binding of specific molecules (biospecificity).