Editing Ramachandran plot

{{Short description|Visual representation of allowable protein conformations}}
[[Image:Ramachandran plot original outlines.jpg|thumb|right|220px|Original hard-sphere, reduced-radius, and relaxed-tau φ,ψ regions from Ramachandran, with updated labels and axes]]
[[Image:Protein backbone PhiPsiOmega drawing.svg|thumb|left|140px|Backbone dihedral angles φ and ψ (and ω). All three angles are at 180° in the conformation shown]]
In [[biochemistry]], a '''Ramachandran plot''' (also known as a '''Rama plot''', a '''Ramachandran diagram''' or a '''[φ,ψ] plot'''), originally developed in 1963 by [[Gopalasamudram Narayana Ramachandran|G. N. Ramachandran]], C. Ramakrishnan, and [[V. Sasisekharan]],<ref>{{cite journal |pages=95–9 |doi=10.1016/S0022-2836(63)80023-6 |title=Stereochemistry of polypeptide chain configurations |year=1963 |last1=Ramachandran |first1=G.N. |last2=Ramakrishnan |first2=C. |last3=Sasisekharan |first3=V. |journal=Journal of Molecular Biology |volume=7 |pmid=13990617}}</ref> is a way to visualize energetically allowed regions for backbone [[dihedral angle]]s ( also called as torsional angles , phi and psi angles ) ψ against φ of [[amino acid]] residues in [[protein structure]]. The figure on the left illustrates the definition of the φ and ψ backbone dihedral angles<ref>{{cite book |year=1981 |last1=Richardson |first1=J.S. |title=Anatomy and Taxonomy of Protein Structures |chapter=The Anatomy and Taxonomy of Protein Structure |volume=34 |pages=167–339 |doi=10.1016/S0065-3233(08)60520-3 |pmid=7020376 |series=Advances in Protein Chemistry |isbn=9780120342341}}</ref> (called φ and φ' by Ramachandran). The ω angle at the [[peptide bond]] is normally 180°, since the partial-double-bond character keeps the peptide bond planar.<ref>{{cite journal | year= 1951 |last1= Pauling |first1=L. |last2=Corey |first2=H.R. |last3=Branson |title= The Structure of Proteins: Two Hydrogen-Bonded Helical Configurations of the Polypeptide Chain |journal= Proceedings of the National Academy of Sciences of the United States of America|volume= 37|pages= 205–211 |pmc = 1063337 |pmid=14816373 |issue=4 |doi=10.1073/pnas.37.4.205 | first3= H. R.|bibcode=1951PNAS...37..205P |doi-access= free }}</ref> The figure in the top right shows the allowed φ,ψ backbone conformational regions from the Ramachandran et al. 1963 and 1968 hard-sphere calculations: full radius in solid outline, reduced radius in dashed, and relaxed tau (N-Cα-C) angle in dotted lines.<ref>{{cite book |last1=Ramachandran |first1=G.N. |last2= Sasiskharan |first2=V. |year=1968 |title= Conformation of polypeptides and proteins |volume=23 |pages=283–437 |doi=10.1016/S0065-3233(08)60402-7 |series=Advances in Protein Chemistry |isbn=9780120342235 |pmid=4882249}}</ref> Because [[dihedral angle]] values are circular and 0° is the same as 360°, the edges of the Ramachandran plot "wrap" right-to-left and bottom-to-top. For instance, the small strip of allowed values along the lower-left edge of the plot are a continuation of the large, extended-chain region at upper left. 
[[Image:1axc PCNA ProCheck Rama.jpg|thumb|200px|right| A Ramachandran plot generated from human [[PCNA]], a trimeric [[DNA clamp]] protein that contains both [[Beta sheet|β-sheet]] and [[Alpha helix|α-helix]] ([[Protein Data Bank|PDB]] ID 1AXC). The red, brown, and yellow regions represent the favored, allowed, and "generously allowed" regions, respectively, as defined by ProCheck]]

==Uses==
A Ramachandran plot can be used in two somewhat different ways. One is to show in theory which values, or [[Chemical conformation|conformations]], of the ψ and φ angles are possible for an amino-acid residue in a protein (as at top right). A second is to show the empirical distribution of datapoints observed in a single structure (as at right, here) in usage for [[structure validation]], or else in a database of many structures (as in the lower 3 plots at left). It's used to predict about Drug-ligand interaction and helpful in pharmaceutical industries. Either case is usually shown against outlines for the theoretically favored regions.

==Amino-acid preferences==
One might expect that larger side chains would result in more restrictions and consequently a smaller allowable region in the Ramachandran plot, but the effect of side chains is small.<ref name="chak2001">{{cite journal |last1=Chakrabarti |first1=Pinak |last2=Pal |first2=Debnath |year=2001 |title= The interrelationships of side-chain and main-chain conformations in proteins |journal=Progress in Biophysics and Molecular Biology |volume=76 |pages=1–102 |doi=10.1016/S0079-6107(01)00005-0 |issue=1–2 |pmid=11389934|doi-access=free }}</ref> In practice, the major effect seen is that of the presence or absence of the methylene group at Cβ.<ref name="chak2001" /> [[Glycine]] has only a hydrogen atom for its side chain, with a much smaller [[van der Waals radius]] than the CH<sub>3</sub>, CH<sub>2</sub>, or CH group that starts the side chain of all other amino acids. Hence it is least restricted, and this is apparent in the Ramachandran plot for glycine (see Gly plot in [[#Gallery|gallery]]) for which the allowable area is considerably larger. In contrast, the Ramachandran plot for [[proline]], with its 5-membered-ring side chain connecting Cα to backbone N, shows a limited number of possible combinations of ψ and φ (see Pro plot in [[#Gallery|gallery]]). The residue preceding proline ("pre-proline") also has limited combinations compared to the general case.

==More recent updates==
The first Ramachandran plot was calculated just after the first protein structure at atomic resolution was determined ([[myoglobin]], in 1960<ref>{{cite journal |pages=422–427 |year=1960 |last1=Kendrew |first1=J.C. |last2=Dickerson |first2=R.E. |last3=Strandberg |first3=B.E. |last4=Hart |first4=R.G. |last5=Davies |first5=D.R. |last6=Phillips |first6=D.C. |last7=Shore |first7=V.C. |title=Structure of myoglobin: a three-dimensional Fourier synthesis at 2Å resolution |journal=Nature |volume=185 |doi=10.1038/185422a0 |issue=4711 |pmid=18990802|bibcode=1960Natur.185..422K |s2cid=4167651 }}</ref>), although the conclusions were based on small-molecule crystallography of short peptides. Now, many decades later, there are tens of thousands of high-resolution protein structures determined by X-ray [[crystallography]] and deposited in the [[Protein Data Bank|Protein Data Bank (PDB)]]. Many studies have taken advantage of this data to produce more detailed and accurate φ,ψ plots (e.g., Morris ''et al.'' 1992;<ref name="ProCheck">{{cite journal |pages=345–64 |doi=10.1002/prot.340120407 |title=Stereochemical quality of protein structure coordinates |year=1992 |last1=Morris |first1=A.L. |last2=MacArthur |first2=M.W. |last3=Hutchinson |first3=E G. |last4=Thornton |first4=J.M. |journal=Proteins: Structure, Function, and Genetics |volume=12 |issue=4 |pmid=1579569|s2cid=940786 }}</ref> [[Gerard Kleywegt|Kleywegt]] & Jones 1996;<ref>{{cite journal |pmid=8994966 |year=1996 |last1=Kleywegt |first1=G.J. |last2=Jones |first2=T.A. |title=Phi/psi-chology: Ramachandran revisited |volume=4 |issue=12 |pages=1395–400 |journal=Structure |doi=10.1016/S0969-2126(96)00147-5|doi-access=free }}</ref> Hooft ''et al.'' 1997;<ref>{{cite journal|last1=Hooft|first1=R.W.W.|last2=Sander|first2=C.|last3=Vriend|first3=G.|title=Objectively judging the quality of a protein structure from a Ramachandran plot|journal=Comput Appl Biosci|year=1997|volume=13|issue=4|pages=425–430|doi=10.1093/bioinformatics/13.4.425|pmid=9283757|doi-access=free}}</ref> Hovmöller ''et al.'' 2002;<ref>{{cite journal |pmid=11976487 |year=2002 |last1=Hovmöller |first1=S. |last2=Zhou |first2=T. |last3=Ohlson |first3=T. |title=Conformations of amino acids in proteins |volume=58 |issue=Pt 5 |pages=768–76 |journal=Acta Crystallographica D |url=http://scripts.iucr.org/cgi-bin/paper?S0907444902003359 |doi=10.1107/S0907444902003359|url-access=subscription }}</ref> Lovell ''et al.'' 2003;<ref name="penultLib">{{cite journal |pages=437–50 |doi=10.1002/prot.10286 |title=Structure validation by Cα geometry: ϕ,ψ and Cβ deviation |year=2003 |last1=Lovell |first1=S.C. |last2=Davis |first2=I.W. |last3=Arendall |first3=W.B. |last4=De Bakker |first4=P.I.W. |last5=Word |first5=J.M. |last6=Prisant |first6=M.G. |last7=Richardson |first7=J.S. |last8=Richardson |first8=D.C. |journal=Proteins: Structure, Function, and Genetics |volume=50 |issue=3 |pmid=12557186|s2cid=8358424 }}</ref> Anderson ''et al.'' 2005''.<ref name="pmid16021632">{{cite journal |vauthors=Anderson RJ, Weng Z, Campbell RK, Jiang X | title = Main-chain conformational tendencies of amino acids | journal = Proteins | volume = 60 | issue = 4 | pages = 679–89 | year = 2005 | pmid = 16021632 | doi=10.1002/prot.20530| s2cid = 17410997 }}</ref> Ting ''et al.'' 2010<ref name="ndrd">{{cite journal |pages=e1000763 |title=Neighbor-dependent Ramachandran probability distributions of amino acids developed from a hierarchical Dirichlet process model |year=2010 |last1=Ting |first1=D. |last2=Wang |first2=G. |last3=Mitra |first3=R. |last4=Jordan |first4=M.I. |last5=Dunbrack |first5=R.L. |journal=PLOS Computational Biology |volume=6 |issue=4 |pmid=20442867 |doi=10.1371/journal.pcbi.1000763 |pmc=2861699|bibcode=2010PLSCB...6E0763T |doi-access=free }}</ref>).

The four figures below show the datapoints from a large set of high-resolution structures and contours for favored and for allowed conformational regions for the general case (all amino acids except Gly, Pro, and pre-Pro), for Gly, and for Pro.<ref name="penultLib"/> The most common regions are labeled: α for [[Alpha helix|α helix]], Lα for left-handed helix, β for [[beta sheet|β-sheet]], and ppII for polyproline II. Such a clustering is alternatively described in the ABEGO system, where each letter stands for α (and 3<sub>10</sub>) helix, right-handed β sheets (and extended structures), left-handed helixes, left-handed sheets, and finally unplottable cis peptide bonds sometimes seen with proline; it has been used in the classification of motifs<ref>{{cite journal |last1=Wintjens |first1=René T. |last2=Rooman |first2=Marianne J. |last3=Wodak |first3=Shoshana J. |title=Automatic Classification and Analysis of αα-Turn Motifs in Proteins |journal=Journal of Molecular Biology |date=January 1996 |volume=255 |issue=1 |pages=235–253 |doi=10.1006/jmbi.1996.0020|pmid=8568871 }}</ref> and more recently for designing proteins.<ref>{{cite journal |last1=Lin |first1=Yu-Ru |last2=Koga |first2=Nobuyasu |last3=Tatsumi-Koga |first3=Rie |last4=Liu |first4=Gaohua |last5=Clouser |first5=Amanda F. |last6=Montelione |first6=Gaetano T. |last7=Baker |first7=David |title=Control over overall shape and size in de novo designed proteins |journal=Proceedings of the National Academy of Sciences |date=6 October 2015 |volume=112 |issue=40 |pages=E5478–E5485 |doi=10.1073/pnas.1509508112|pmc=4603489 |pmid=26396255|bibcode=2015PNAS..112E5478L |doi-access=free }}</ref>

While the Ramachandran plot has been a textbook resource for explaining the structural behavior of peptide bond, an exhaustive exploration of how a peptide behaves in every region of the Ramachandran plot was only recently published  (Mannige 2017<ref>{{cite journal|last1=Mannige|first1=Ranjan|title=An exhaustive survey of regular peptide conformations using a new metric for backbone handedness (''h'')|journal=PeerJ|date=16 May 2017|volume=5|page=e3327|doi=10.7717/peerj.3327|pmc=5436576|pmid=28533975 |doi-access=free }}</ref>).

The [[Molecular Biophysics]] Unit at Indian Institute of Science celebrated 50 years of Ramachandran Map<ref>{{cite web|title=50th Anniversary of Ramachandran Plots|url=http://sandwalk.blogspot.in/2013/01/50th-anniversary-of-ramachandran-plots.html|publisher=Professor [[Laurence A. Moran]]|accessdate=17 January 2013}}</ref> by organizing International Conference on Biomolecular Forms and Functions from 8–11 January 2013.<ref>{{cite web|title=ICBFF-2013|url=http://icbff2013.com/|publisher=MBU, IISc, Bangalore|accessdate=28 January 2013|archive-url=https://web.archive.org/web/20130115045506/http://icbff2013.com/|archive-date=15 January 2013|url-status=dead|df=dmy-all}}</ref>

==Related conventions==
One can also plot the dihedral angles in [[polysaccharide]]s (e.g. with [http://glycosciences.de/tools/carp/ CARP] {{Webarchive|url=https://web.archive.org/web/20190505091719/http://www.glycosciences.de/tools/carp/ |date=2019-05-05 }}).<ref>{{cite journal |pmid=15608187 |year=2005 |last1=Lütteke |first1=T. |last2=Frank |first2=M. |last3=von der Lieth |first3=C.W. |title=Carbohydrate Structure Suite (CSS): analysis of carbohydrate 3D structures derived from the PDB |volume=33 |issue=Database issue |pages=D242–246 |journal=Nucleic Acids Res |doi=10.1093/nar/gki013 |pmc=539967}}</ref>

==Gallery==
<gallery>
Image:Ramachandran plot general 100K.jpg|Ramachandran plot for the general case; data from Lovell 2003
Image:Ramachandran plot Gly.jpg|Ramachandran plot for Glycine
Image:Ramachandran plot Pro.jpg|Ramachandran plot for Proline
Image:Ramachandran plot pre-Pro.png|Ramachandran plot for pre-Proline
</gallery>

==Software==
*[http://tomcat.cs.rhul.ac.uk/home/mxba001/ Web-based Structural Analysis tool for any uploaded PDB file, producing Ramachandran plots, computing dihedral angles and extracting sequence from PDB] {{Webarchive|url=https://web.archive.org/web/20160305042525/http://tomcat.cs.rhul.ac.uk/home/mxba001/ |date=2016-03-05 }}
*[https://web.archive.org/web/20090726062008/http://www.fos.su.se/~pdbdna/input_Raman.html Web-based tool showing Ramachandran plot of any PDB entry]
*[http://molprobity.biochem.duke.edu MolProbity web service that produces Ramachandran plots and other validation of any PDB-format file]
*[http://services.mbi.ucla.edu/SAVES SAVES] (Structure Analysis and Verification) &mdash; uses WHATCHECK, PROCHECK, and does its own internal Ramachandran Plot 
*[[STING]]
*[[Pymol]] with the DynoPlot extension
*[[Visual Molecular Dynamics|VMD]], distributed with dynamic Ramachandran plot plugin
*[[WHAT CHECK]], the stand-alone validation routines from the [[WHAT IF software]]
*[[UCSF Chimera]], found under the Model Panel.
*[[Sirius visualization software|Sirius]]
*[https://spdbv.vital-it.ch/ Swiss PDB Viewer]
*[http://spin.niddk.nih.gov/NMRPipe/talos/ TALOS]
*[http://www.al-nasir.com/www/Jamie/Zeus/ Zeus molecular viewer] &mdash; found under "Tools" menu, high quality plots with regional contours
*[http://www.ebi.ac.uk/thornton-srv/software/PROCHECK/ Procheck]
*[http://dunbrack.fccc.edu/ndrd Neighbor-Dependent and Neighbor-Independent Ramachandran Probability Distributions]<ref name="ndrd"/>
*See also [[Protein Data Bank#Molecular graphic visualisation tools|PDB]] for a list of similar software.

==References==
{{reflist|2}}

==Further reading==
* {{cite book |year=1981 |last1=Richardson |first1=J.S. |title=Anatomy and Taxonomy of Protein Structures |chapter=The Anatomy and Taxonomy of Protein Structure |volume=34 |pages=167–339 |doi=10.1016/S0065-3233(08)60520-3 |pmid=7020376 |series=Advances in Protein Chemistry |isbn=9780120342341}}, available on-line at [http://kinemage.biochem.duke.edu/Anatax Anatax]{{dead link|date=April 2018 |bot=InternetArchiveBot |fix-attempted=yes }}
* {{citation |year=1991 |last1=Branden |first1=C.-I. |last2=Tooze |first2=J. |title=Introduction to Protein Structure |publisher=Garland Publishing, NY |isbn=0-8153-0344-0 }}

==External links==
{{Commons category|Ramachandran plot}}
*[http://wiki.pymol.org/index.php/DynoPlot DynoPlot in PyMOL wiki]
*[http://www.cryst.bbk.ac.uk/PPS95/course/3_geometry/rama.html Link to Ramachandran Plot Map of alpha-helix and beta-sheet locations] {{Webarchive|url=https://web.archive.org/web/20061011174159/http://www.cryst.bbk.ac.uk/PPS95/course/3_geometry/rama.html |date=2006-10-11 }}
*[http://www.fos.su.se/~svenh/index.html Link to Ramachandran plot calculated from protein structures determined by X-ray crystallography compared to the original Ramachan.]
*[http://www.proteopedia.org/wiki/index.php/Ramachandran_Plot ''Proteopedia'' Ramachandran Plot]

[[Category:Biochemistry methods]]
[[Category:Plots (graphics)]]