Editing Alpha helix (section)

== Structure ==

=== Geometry and hydrogen bonding ===
The amino acids in an α-helix are arranged in a right-handed [[helix|helical]] structure where each amino acid residue corresponds to a 100° turn in the helix (i.e., the helix has 3.6 residues per turn), and a translation of {{cvt|1.5|Å|nm}} along the helical axis. Dunitz<ref>{{cite journal | vauthors = Dunitz J | author-link = Jack Dunitz | year = 2001 | title = Pauling's Left-Handed α-Helix | journal = Angewandte Chemie International Edition | volume = 40 | pages = 4167&ndash;4173 | doi = 10.1002/1521-3773(20011119)40:22<4167::AID-ANIE4167>3.0.CO;2-Q | issue = 22| pmid = 29712120 }}</ref> describes how Pauling's first article on the theme in fact shows a left-handed helix, the enantiomer of the true structure. Short pieces of left-handed helix sometimes occur with a large content of achiral [[glycine]] amino acids, but are unfavorable for the other normal, biological [[amino acids|{{small|L}}-amino acids]]. The pitch of the alpha-helix (the vertical distance between consecutive turns of the helix) is {{cvt|5.4|Å|nm}}, which is the product of 1.5 and 3.6. The most important thing is that the [[amine|N-H]] group of one amino acid forms a [[hydrogen bond]] with the [[carbonyl|C=O]] group of the amino acid ''four'' residues earlier; this repeated ''i''&nbsp;+&nbsp;4 → ''i'' hydrogen bonding is the most prominent characteristic of an α-helix. Official international nomenclature<ref>{{cite journal | author = IUPAC-IUB Commission on Biochemical Nomenclature | year = 1970 | title = Abbreviations and symbols for the description of the conformation of polypeptide chains | journal = Journal of Biological Chemistry | volume = 245 | issue = 24 | pages = 6489–6497| doi = 10.1016/S0021-9258(18)62561-X | doi-access = free }}</ref><ref name="qmul_ppep1">{{cite web |title=Polypeptide Conformations 1 and 2 |url=http://www.sbcs.qmul.ac.uk/iupac/misc/ppep1.html |website=www.sbcs.qmul.ac.uk |access-date=5 November 2018}}</ref> specifies two ways of defining α-helices, rule 6.2 in terms of repeating ''φ'', ''ψ'' torsion angles (see below) and rule 6.3 in terms of the combined pattern of pitch and hydrogen bonding. The α-helices can be identified in protein structure using several computational methods, such as [[DSSP (algorithm)|DSSP]] (Define&nbsp;[[Secondary structure|Secondary Structure]] of Protein).<ref>{{cite journal | vauthors = Kabsch W, Sander C | title = Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features | journal = Biopolymers | volume = 22 | issue = 12 | pages = 2577–637 | date = December 1983 | pmid = 6667333 | doi = 10.1002/bip.360221211 | s2cid = 29185760 }}</ref>

[[Image:Alpha vs 310 helix end views.jpg|thumb|left|300px|Contrast of helix end views between α (offset squarish) vs 3<sub>10</sub> (triangular)]]
Similar structures include the [[310 helix|3<sub>10</sub> helix]] (''i''&nbsp;+&nbsp;3 → ''i'' hydrogen bonding) and the [[Pi helix|π-helix]] (''i''&nbsp;+&nbsp;5 → ''i'' hydrogen bonding). The α-helix can be described as a 3.6<sub>13</sub> helix, since the ''i''&nbsp;+&nbsp;4 spacing adds three more atoms to the H-bonded loop compared to the tighter 3<sub>10</sub> helix, and on average, 3.6 amino acids are involved in one ring of α-helix. The subscripts refer to the number of atoms (including the hydrogen) in the closed loop formed by the hydrogen bond.<ref name="Anatax">{{cite journal | vauthors = Richardson JS | title = The anatomy and taxonomy of protein structure | journal = Advances in Protein Chemistry | volume = 34 | pages = 167–339 | year = 1981 | pmid = 7020376 | doi = 10.1016/S0065-3233(08)60520-3 | author-link = Jane S. Richardson | isbn = 9780120342341 }}</ref>

[[Image:Ramachandran plot general 100K.jpg|thumb|right|250px|[[Ramachandran plot]] (''φ'',&nbsp;''ψ'' plot), with data points for α-helical residues forming a dense diagonal cluster below and left of center, around the global energy minimum for backbone conformation.<ref>{{cite journal | vauthors = Lovell SC, Davis IW, Arendall WB, de Bakker PI, Word JM, Prisant MG, Richardson JS, Richardson DC | title = Structure validation by Calpha geometry: phi,psi and Cbeta deviation | journal = Proteins | volume = 50 | issue = 3 | pages = 437–50 | date = February 2003 | pmid = 12557186 | doi = 10.1002/prot.10286 | s2cid = 8358424 }}</ref>]]
Residues in α-helices typically adopt backbone (''φ'',&nbsp;''ψ'') [[dihedral angle]]s around (−60°,&nbsp;−45°), as shown in the image at right. In more general terms, they adopt dihedral angles such that the ''ψ'' dihedral angle of one residue and the ''φ'' dihedral angle of the ''next'' residue sum to roughly −105°. As a consequence, α-helical dihedral angles, in general, fall on a diagonal stripe on the [[Ramachandran diagram]] (of slope −1), ranging from (−90°,&nbsp;−15°) to (−70°,&nbsp;−35°). For comparison, the sum of the dihedral angles for a 3<sub>10</sub> helix is roughly −75°, whereas that for the π-helix is roughly −130°. The general formula for the rotation angle ''Ω'' per residue of any polypeptide helix with ''trans'' isomers is given by the equation<ref>{{citation | vauthors = Dickerson RE, Geis I | author-link2 = Irving Geis |  year = 1969 | title = Structure and Action of Proteins | publisher = Harper, New York }}</ref><ref>{{cite book|chapter = Structural Organization of Proteins|first = Matjaž|last = Zorko|pages = 36–57|title = Introduction to Peptides and Proteins|editor1-first = Ülo|editor1-last = Langel|editor2-first = Benjamin F.|editor2-last = Cravatt|editor-link2 = Benjamin Cravatt III|editor3-first = Astrid|editor3-last = Gräslund|editor4-first = Gunnar|editor4-last = von Heijne|editor-link4 = Gunnar von Heijne|editor7-first = Matjaž|editor7-last = Zorko|editor5-first = Tiit|editor5-last = Land|editor6-first = Sherry|editor6-last = Niessen|publisher = [[CRC Press]]|location = Boca Raton|year = 2010|chapter-url = https://books.google.com/books?id=GA3SBQAAQBAJ&pg=PA40|isbn = 9781439882047}}</ref>

:{{math|3 cos ''Ω'' {{=}} 1 − 4 cos<sup>2</sup> {{sfrac|''φ'' + ''ψ''|2}}}}

The α-helix is tightly packed; there is almost no free space within the helix. The amino-acid side-chains are on the outside of the helix, and point roughly "downward" (i.e., toward the N-terminus), like the branches of an evergreen tree ([[Christmas tree]] effect). This directionality is sometimes used in preliminary, low-resolution electron-density maps to determine the direction of the protein backbone.<ref>{{cite journal | vauthors = Terwilliger TC | title = Rapid model building of alpha-helices in electron-density maps | journal = Acta Crystallographica Section D | volume = 66 | issue = Pt 3 | pages = 268–75 | date = March 2010 | pmid = 20179338 | pmc = 2827347 | doi = 10.1107/S0907444910000314 | bibcode = 2010AcCrD..66..268T }}</ref>

=== Stability ===
{{See also|Stapled peptide}}
Helices observed in proteins can range from four to over forty residues long, but a typical helix contains about ten amino acids (about three turns). In general, short [[polypeptide]]s do not exhibit much α-helical structure in solution, since the [[entropy|entropic]] cost associated with the folding of the polypeptide chain is not compensated for by a sufficient amount of stabilizing interactions. In general, the backbone [[hydrogen bond]]s of α-helices are considered slightly weaker than those found in [[beta sheet|β-sheets]], and are readily attacked by the ambient water molecules. However, in more hydrophobic environments such as the [[cellular membrane|plasma membrane]], or in the presence of co-solvents such as [[trifluoroethanol]] (TFE), or isolated from solvent in the gas phase,<ref>{{cite journal | vauthors = Hudgins RR, Jarrold MF | year = 1999 | title = Helix Formation in Unsolvated Alanine-Based Peptides: Helical Monomers and Helical Dimers | journal = Journal of the American Chemical Society | volume = 121 | pages = 3494&ndash;3501 | doi = 10.1021/ja983996a | issue = 14}}</ref> oligopeptides readily adopt stable α-helical structure.  Furthermore, crosslinks can be incorporated into peptides to conformationally stabilize helical folds.  Crosslinks stabilize the helical state by entropically destabilizing the unfolded state and by removing enthalpically stabilized "decoy" folds that compete with the fully helical state.<ref>{{cite journal | vauthors = Kutchukian PS, Yang JS, Verdine GL, Shakhnovich EI | title = All-atom model for stabilization of alpha-helical structure in peptides by hydrocarbon staples | journal = Journal of the American Chemical Society | volume = 131 | issue = 13 | pages = 4622–7 | date = April 2009 | pmid = 19334772 | pmc = 2735086 | doi = 10.1021/ja805037p }}</ref> It has been shown that α-helices are more stable, robust to mutations and designable than β-strands in natural proteins,<ref>{{cite journal | vauthors = Abrusan G, Marsh JA | title = Alpha helices are more robust to mutations than beta strands | journal = PLOS Computational Biology | volume = 12 | issue = 12 | pages = e1005242 | date = 2016 | pmid = 27935949 | doi = 10.1371/journal.pcbi.1005242 | bibcode = 2016PLSCB..12E5242A | pmc=5147804 | doi-access = free }}</ref> and also in artificially designed proteins.<ref>{{cite journal | vauthors = Rocklin GJ et al. | title = Global analysis of protein folding using massively parallel design, synthesis, and testing | journal = Science | volume = 357 | issue = 6347 | pages = 168–175 | date = 2017 | pmid = 28706065 | doi = 10.1126/science.aan0693 | bibcode = 2017Sci...357..168R | pmc=5568797}}</ref>

[[Image:Helix electron density myoglobin 2nrl 17-32.jpg|thumb|right|200px|An α-helix in ultrahigh-resolution electron density contours, with oxygen atoms in red, nitrogen atoms in blue, and hydrogen bonds as green dotted lines (PDB file 2NRL, 17–32). The N-terminus is at the top, here.]]

=== Visualization ===

The three most popular ways of visualizing the alpha-helical secondary structure of oligopeptide sequences are (1) a [[helical wheel]],<ref>{{cite journal | vauthors = Schiffer M, Edmundson AB | title = Use of helical wheels to represent the structures of proteins and to identify segments with helical potential | journal = Biophysical Journal | volume = 7 | issue = 2 | pages = 121–135 | date = 1967 | doi = 10.1016/S0006-3495(67)86579-2| pmid = 6048867 | pmc = 1368002 | bibcode = 1967BpJ.....7..121S }}</ref> (2) a wenxiang diagram,<ref>{{cite journal | vauthors = Chou KC, Zhang CT, Maggiora GM | title = Disposition of amphiphilic helices in heteropolar environments | journal = Proteins: Structure, Function, and Genetics | volume = 28 | pages = 99–108 | date = 1997| issue = 1 | doi = 10.1002/(SICI)1097-0134(199705)28:1<99::AID-PROT10>3.0.CO;2-C | pmid = 9144795 | s2cid = 26944184 }}</ref> and (3) a helical net.<ref>{{cite journal | vauthors = Dunnill P | title = The Use of Helical Net-Diagrams to Represent Protein Structures | journal = Biophysical Journal | volume = 8 | issue = 7 | pages = 865–875 | date = 1968 | pmid = 5699810 | pmc = 1367563 | doi = 10.1016/S0006-3495(68)86525-7| bibcode = 1968BpJ.....8..865D }}</ref> Each of these can be visualized with various software packages and web servers. To generate a small number of diagrams, Heliquest<ref>{{cite journal | vauthors = Gautier R, Douguet D, Antonny B, Drin G | title = HELIQUEST: a web server to screen sequences with specific alpha-helical properties | journal = Bioinformatics | volume = 24 | issue = 18 | pages = 2101–2102 | date = 2008 | doi = 10.1093/bioinformatics/btn392| pmid = 18662927 | doi-access = free }}</ref> can be used for helical wheels, and NetWheels<ref>{{cite journal | vauthors = Mol AR, Castro MS, Fontes W | title = NetWheels: A web application to create high quality peptide helical wheel and net projections | journal = bioRxiv | date = 2018 | doi = 10.1101/416347| s2cid = 92137153 }}</ref> can be used for helical wheels and helical nets. To programmatically generate a large number of diagrams, helixvis<ref>{{cite journal | vauthors = Wadhwa RR, Subramanian V, Stevens-Truss R | title = Visualizing alpha-helical peptides in R with helixvis | journal = Journal of Open Source Software | volume = 3 | issue = 31 | pages = 1008 | date = 2018 | doi = 10.21105/joss.01008| bibcode = 2018JOSS....3.1008W | s2cid = 56486576 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Subramanian V, Wadhwa RR, Stevens-Truss R | title = Helixvis: Visualize alpha-helical peptides in Python | journal = ChemRxiv | date = 2020}}</ref> can be used to draw helical wheels and wenxiang diagrams in the R and Python programming languages.