Editing Structural bioinformatics (section)

== Introduction ==

=== Protein structure ===
{{main|Protein structure}}
The structure of a protein is directly related to its function. The presence of certain chemical groups in specific locations allows proteins to act as [[enzyme]]s, catalyzing several chemical reactions.<ref>{{Cite book|last1=Gu|first1=Jenny |last2=Bourne|first2=Philip E. | name-list-style = vanc |url=https://books.google.com/books?id=4H_ai7ivRIcC|title=Structural Bioinformatics|date=2009-03-16|publisher=John Wiley & Sons|isbn=978-0-470-18105-8|language=en}}</ref> In general, protein structures are classified into four levels: [[Protein primary structure|primary]] (sequences), [[Protein secondary structure|secondary]] (local conformation of the polypeptide chain), [[Protein tertiary structure|tertiary]]  (three-dimensional structure of the protein fold), and [[Protein quaternary structure|quaternary]] (association of multiple polypeptide structures). Structural bioinformatics mainly addresses interactions among structures taking into consideration their space coordinates. Thus, the primary structure is better analyzed in traditional branches of bioinformatics. However, the sequence implies restrictions that allow the formation of conserved local conformations of the polypeptide chain, such as [[alpha-helix]], [[Beta sheet|beta-sheets]], and loops (secondary structure<ref>{{cite journal | vauthors = Kocincová L, Jarešová M, Byška J, Parulek J, Hauser H, Kozlíková B | title = Comparative visualization of protein secondary structures | journal = BMC Bioinformatics | volume = 18 | issue = Suppl 2 | pages = 23 | date = February 2017 | pmid = 28251875 | pmc = 5333176 | doi = 10.1186/s12859-016-1449-z | doi-access = free }}</ref>). Also, weak interactions (such as [[hydrogen bond]]s) stabilize the protein fold. Interactions could be intrachain, i.e., when occurring between parts of the same protein monomer (tertiary structure), or interchain, i.e., when occurring between different structures (quaternary structure). Finally, the topological arrangement of interactions, whether strong or weak, and entanglements is being studied in the field of structural bioinformatics, utilizing frameworks such as [[circuit topology]].

=== Structure visualization ===
[[File:2LZM.png|thumb|300x300px|Structural visualization of BACTERIOPHAGE T4 LYSOZYME (PDB ID: 2LZM). (A) Cartoon; (B) Lines; (C) Surface; (D) Sticks.]]
Protein structure visualization is an important issue for structural bioinformatics.<ref>{{cite journal | vauthors = Shi M, Gao J, Zhang MQ | title = Web3DMol: interactive protein structure visualization based on WebGL | journal = Nucleic Acids Research | volume = 45 | issue = W1 | pages = W523–W527 | date = July 2017 | pmid = 28482028 | pmc = 5570197 | doi = 10.1093/nar/gkx383 }}</ref> It allows users to observe static or dynamic representations of the molecules, also allowing the detection of interactions that may be used to make inferences about molecular mechanisms. The most common types of visualization are:

* '''Cartoon''': this type of protein visualization highlights the secondary structure differences. In general, [[Alpha helix|α-helix]] is represented as a type of screw, [[Beta sheet|β-strands]] as arrows, and [[Loop (biochemistry)|loop]]s as lines.
* '''Lines''': each amino acid residue is represented by thin lines, which allows a low cost for graphic rendering.
* '''Surface''': in this visualization, the external shape of the molecule is shown. 
* '''Sticks''': each covalent bond between amino acid atoms is represented as a stick. This type of visualization is most used to visualize interactions between [[amino acid]]s...

=== DNA structure ===
The classic [[DNA]] duplexes structure was initially described by [[Watson and Crick]] (and contributions of [[Rosalind Franklin]]). The DNA molecule is composed of three substances: a [[phosphate]] group, a [[pentose]], and a nitrogen base ([[adenine]], [[thymine]], [[cytosine]], or [[guanine]]). The DNA double helix structure is stabilized by hydrogen bonds formed between base pairs: adenine with thymine (A-T) and cytosine with guanine (C-G). Many structural bioinformatics studies have focused on understanding interactions between DNA and small molecules, which has been the target of several drug design studies.

=== Interactions ===
Interactions are contacts established between parts of molecules at different levels. They are responsible for stabilizing protein structures and perform a varied range of activities. In [[biochemistry]], interactions are characterized by the proximity of atom groups or molecules regions that present an effect upon one another, such as [[electrostatic forces]], [[hydrogen bond]]ing, and [[hydrophobic effect]]. Proteins can perform several types of interactions, such as [[Protein–protein interaction|protein-protein interactions (PPI)]], protein-peptide interactions'''<ref>{{cite journal | vauthors = Stanfield RL, Wilson IA | title = Protein-peptide interactions | journal = Current Opinion in Structural Biology | volume = 5 | issue = 1 | pages = 103–13 | date = February 1995 | pmid = 7773739 | doi = 10.1016/0959-440X(95)80015-S }}</ref>''', protein-ligand interactions (PLI)'''<ref>{{cite book|title=Drug Design|vauthors=Klebe G|date=2015|publisher=Springer|isbn=978-3-642-17906-8|veditors=Scapin G, Patel D, Arnold E|series=NATO Science for Peace and Security Series A: Chemistry and Biology|location=Dordrecht|pages=83–92|chapter=Protein–Ligand Interactions as the Basis for Drug Action|doi=10.1007/978-3-642-17907-5_4}}</ref>''', and protein-DNA interaction.[[File:Contacts between two amino acid residues- Q196-R200 (PDB ID- 2X1C).png|thumb|Contacts between two amino acid residues: Q196-R200 (PDB ID- 2X1C)<ref>{{Cite web|url=http://proteus.dcc.ufmg.br/|title=Proteus {{!}} PROTein Engineering Supporter {{!}}|website=proteus.dcc.ufmg.br|access-date=2020-02-26}}</ref>|alt=|right]]

=== Calculating contacts ===
Calculating contacts is an important task in structural bioinformatics, being important for the correct prediction of protein structure and folding, thermodynamic stability, protein-protein and protein-ligand interactions, docking and molecular dynamics analyses, and so on.<ref name=":0">{{Cite book| vauthors = Martins PM, Mayrink VD, de Silveira S, da Silveira CH, de Lima LH, de Melo-Minardi RC |title=Proceedings of the 33rd Annual ACM Symposium on Applied Computing |chapter=How to compute protein residue contacts more accurately? |date=2018|chapter-url=http://dl.acm.org/citation.cfm?doid=3167132.3167136|language=en|location=Pau, France|publisher=ACM Press|pages=60–67|doi=10.1145/3167132.3167136|isbn=978-1-4503-5191-1|s2cid=49562347}}</ref>

Traditionally, computational methods have used threshold distance between atoms (also called cutoff) to detect possible interactions.<ref>{{cite journal | vauthors = da Silveira CH, Pires DE, Minardi RC, Ribeiro C, Veloso CJ, Lopes JC, Meira W, Neshich G, Ramos CH, Habesch R, Santoro MM | display-authors = 6 | title = Protein cutoff scanning: A comparative analysis of cutoff dependent and cutoff free methods for prospecting contacts in proteins | journal = Proteins | volume = 74 | issue = 3 | pages = 727–43 | date = February 2009 | pmid = 18704933 | doi = 10.1002/prot.22187 | s2cid = 1208256 | url = http://ainfo.cnptia.embrapa.br/digital/bitstream/item/147896/1/Proteins-Structure-Function-and-Bioinformatics.pdf }}</ref> This detection is performed based on Euclidean distance and angles between atoms of determined types. However, most of the methods based on simple Euclidean distance cannot detect occluded contacts. Hence, cutoff free methods, such as [[Delaunay triangulation]], have gained prominence in recent years. In addition, the combination of a set of criteria, for example, physicochemical properties, distance, geometry, and angles, have been used to improve the contact determination.<ref name=":0" /> 
{| class="wikitable"
|+Distance criteria for contact definition<ref name=":0" />
!Type
!Max distance criteria
|-
|Hydrogen bond
|3,9 Å
|-
|Hydrophobic interaction
|5 Å
|-
|Ionic interaction
|6 Å
|-
|Aromatic Stacking
|6 Å
|}