WHAT IS MC-FOLD | MC-SYM ?

The MC-Fold | MC-Sym pipeline is a web-hosted service for RNA secondary and tertiary structure prediction. The pipeline means that the input sequence to MC-Fold outputs secondary structures that are direct input to MC-Sym, which outputs tertiary structures. The vertical bar '|' is the symbol indicating pipeline processing in Unix, which was invented by Malcolm D. McIlroy. Reference: Parisien M, Major F. Nature. (2008) 452:51-55. (pubmed) (Nature) (user's guide)

WHAT IS MC-FOLD ?

MC-Fold predicts secondary structures from sequence (black arrow). Compared to classical secondary structures that include the AU, CG, and Wobble GU base pairs that form the stems of the structure, MC-Fold's secondary structures include the other base pairing patterns as well. These are often called non-canonical base pairs. ⊕ MC-Fold's database folder ⊕ MC-Fold's user's guide Reference: Parisien and Major. Nature (Supplementary Information)

MC-Fold :: sequence -> [secondary-structure]

Link to MC-Fold


♦ MC-Fold is available online via command line using the cURL program:

curl -Y 0 -y 300 -F "pass=lucy" -F "sequence=CCAGAUCUGAGCCUGGGAGCUCUCUGG" https://www.major.iric.ca/cgi-bin/MC-Fold/mcfold.static.cgi


♦ Compare the results of different secondary structure prediction programs using the following sequences:

• HIV-1 TAR RNA: CCAGAUCUGAGCCUGGGAGCUCUCUGG
• IRE with V-bulge: AUUAUCGGGAGCAGUGUCUUCCAUAAU
• IRE with W-bulge: AUUCUUGCUUCAACAGUGUUUGAACGGAA
• Rat 28S E-loop: GGGUGCUCAGUACGAGAGGAACCGCACCC
• C27A ScYLV pseudoknot: AGUGGCGCCGACCACUUAAAAACAACGG

♦ Alternative secondary structure prediction programs:

• ILM   Ruan, Stormo, Zhang. NAR 2004.
• Sfold   Ding, Lawrence. NAR 2003.
• Pfold   Knudsen, Hein. NAR 2003.
• Mfold   Zuker. NAR 2003.
• VSfold   Dawson, Fujiwara, Kawai. PLoS One 2007.
• RNAfold   Hofacker. NAR 2003.
• CONTRAfold   Do, Woods, Batzoglou. Bioinformatics 2006.
• RNAstructure   Mathews et al. PNAS 2004.

WHAT IS MC-SYM ?

MC-Sym builds tertiary structures from MC-Fold's secondary structures, which are provided as ASCII input scripts. No interactive computer graphics is needed. MC-Sym explores exhaustively or probabilistically the conformational search space of an RNA and produces structures that satisfies all input constraints. ⊕ MC-Sym's FAQ ⊕ MC-Sym's user's guide ⊕ MC-Sym's database folder ⊕ MC-Sym's database snapshot References: Major et al. Science 1991. Major. Comp Sci Eng 2003.

MC-Sym :: secondary-structure -> [tertiary-structure]

Link to MC-Sym


♦ Here is a list of MC-Sym input scripts and PDB references:

PDB ID		MC-Sym		Reference		Type		Description
430D		430D.mcc		430D01.pdb		Hairpin		Rat 28S Loop E
1NBR		1NBR.mcc		1NBR01.pdb		Hairpin		Iron Responsive Element V-form
2HUA		2HUA.mcc		2HUA01.pdb		Hairpin		SCFV IRES Domain III
2GIO		2GIO.mcc		2GIO01.pdb		Hairpin		RNA Thermometer
2FDT		2FDT.mcc		2FDT01.pdb		Hairpin		UnaL2 Interspersed Element
2FEY		2FEY.mcc		2FEY01.pdb		Hairpin		Telomerase RNA Domain IV
2CD1		2CD1.mcc		2CD101.pdb		Hairpin		RNase P RNA P4
2EVY		2EVY.mcc		2EVY01.pdb		Hairpin		GNYA Tetraloop
2O33		2O33.mcc		2O3301.pdb		Hairpin		U2 snRNA
2AHT		2AHT.mcc		2AHT01.pdb		Hairpin		Group II Intron Branchsite
1NYI		1NYI.mcc		1NYI01.pdb		Y-Shape		Hammerhead Ribozyme
2HGH		2HGH.mcc		2HGH01.pdb		Y-Shape		5S rRNA
2AP5		2AP5.mcc		2AP501.pdb		Pseudoknot		Yellow Leaf Virus
2P89		[P1] [P1S] [P2] [P2S]		2P8901.pdb		Complex		H/ACA Box
		[Whole]

WHAT IS MC-CONS ?

MC-Cons assigns a secondary structure for each sequence among the sequence's set of sub-optimal secondary structures, such that the set of assigned secondary structures maximizes the sum of pairwise structural similarity; the consensus assignment. MC-Cons can be seen as a filter between multiple-sequences and tertiary structure. ⊕ MC-Cons's user's guide Reference: Parisien and Major. Nature (Supplementary Information)

MC-Cons :: [(sequence, [secondary-structure])] -> [(sequence, secondary-structure)]

Link to MC-Cons


♦ Alternative consensus structure and assignment programs:

• Marna (MC-Fold output friendly)   Siebert, Backofen. Bioinformatics 2005.
• RNAshapes (sequence data only)   Steffen et al. Bioinformatics 2006.

DOT-BRACKET RENDERING

A tool for rendering dot-bracket structures is plot_rna of the CONTRAfold package (Do et al. Bioinformatics 2006).

Type or paste in your dot-bracket structures: Index of the first nucleotide:

Here is an input example:

>ce TrxR
GACCUUUGGCUAAACUCCAUCGUGAGCGCCUCUGGUC
((((((((((..((((((...))))))))))))))))   -32.465
((((((((((...(((((...).))))))))))))))   -32.570

♦ Alternative rendering programs with pseudoknot capability:

• PseudoViewer   Byun, Han. NAR 2006. (online web server)
• jViz.Rna   Wiese, Glen. IEEE CBSM 2006. (manual adjustments)

MC-SYM SCRIPT GENERATOR

This program will generate an MC-Sym script that will build an RNA of the specified sequence and secondary structure. Please consider these points:

• Accepted symbols for sequence are: `A`, `C`, `G`, `U` and `T`.
• Accepted symbols for structure are: `.`, `(`, `[`, `)` and `]`.
• Isolated base pairs .(. .). are not modeled if they are not within NCMs.
• Structures with more than 40% in single-stranded (i.e. non-structures) are not modeled.
• Classic secondary structures are difficult to model properly.
• Pseudoknots are accepted, as long as the expression is properly balanced.
• For advanced modeling topics please visit our FAQ.

Type or paste in your sequence followed by your dot-bracket structure: Clicking Submit will queue this job on the MC-Sym web server. Clicking Advanced will bring a web page of options. Please use with parsimony and good judgment!

Here is an input example:

>ce TrxR
GACCUUUGGCUAAACUCCAUCGUGAGCGCCUCUGGUC
((((((((((..((((((...))))))))))))))))

Here is another input example, with a pseudoknot:

>2TPK
UGACCAGCUAUGAGGUCAUACAUCGUCAUAGC
(((((.[[[[[[[))))).......]]]]]]]

RNA DOUBLE-HELIX GENERATOR

This program will generate an MC-Sym script that will build an RNA double-helix.

1. Sequence  An empty 3'-strand field indicates A=U/C=G double helix The 3'-strand sequence must be entered 3' to 5'   strand 5'-    strand 3'-

♦ Alternative double-helix generators:

• PREDICTOR (DNA double-helix) Farwer et al. In Silico Biol 2007. (online web server)

RNA INTERACTION NETWORK FIDELITY

This program will calculate the interaction network fidelity (INF) between two RNA 3-D structures based on their annotations.

1. Structures  Locate your reference and your model files Files should be in the PDB format Files cannot be compressed Structures should have the same chain IDs and numberings   Reference:    Model:    Method: MC-Annotate [1,2,3,4,5]     RNAview [1,6]     Consider stacking too! [3,4,5]             [1] Leontis & Westhof. RNA. 2001     [2] Lemieux & Major. Nucleic Acids Res. 2002     [3] Gabb et al. J Mol Graph. 1996     [4] Major & Thibault. in Bioinformatics: From Genomes to Therapies. 2007     [5] Gendron et al. J Mol Biol. 2001     [6] Yang et al. Nucleic Acids Res. 2003

RNA SEQUENCE MUTATION

This program will mutate the nucleobase identity to the specified sequence into the furnished 3D structure. This is useful to perform point mutations in a structure, or to replace non-canonical nucleobases by standard one.

1. Sequence and Structure  Locate your structure, specified in the PDB file format. The structure should be stripped of all ions and water molecules. The sequence progresses from the 5'-end to the 3'-end.   Structure:    Sequence:

Here is an input example:

Structure: PDB file 1EVV (without ions and water molecules).
Sequence:  GCGGAUUUAGCUCAGUUGGGAGAGCGCCAGACUGAAGAUCUGGAGGUCCUGUGUUCGAUCCACAGAAUUCGCACCA

CONTACT

Link to the RNA Engineering Lab Link to Francois Major Link to Marc Parisien Many thanks to Patrick Gendron for managing Condor at the IRIC bioinformatics plateform and for helping us out with the distributed computation issues!

created: October 16, 2007
updated: August 05, 2009