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GERF Bulletin of Biosciences 2010, 1(1): 51-54

Software Review

Mfold©: RNA modeling program

Authors: Prof: Michael Zuker, Professor of mathematical sciences;
License: Freeware, Copyright © Washington University.
Reviewed By: Dr. Ahmed Mansour Alzohairy
Genetic Department, Faculty of Agriculture, Zagazig University, Egypt.

Mfold at a glace journals, Mfold become very important bioinformatics

RNA structure is very important in many biological software in molecular biology for prediction of secondary
processes, including translation regulation in messenger RNA structure. The freeware license and its efficient up to
RNA and replication of single-stranded RNA viruses. Much date modules beside its quick ability to produce results make
of Michel Zuker work is on studying RNA structure. He it one of the most popular programs predicting secondary
developed Mfold program as tool for predicting the secondary structure of RNA of nowadays.
structure of RNA, mainly by using thermodynamic methods
Advantages and Disadvantages of Mfold
(the Gibbs free energy). That sophisticated RNA modeling
program takes into account many parameters, (e.g. pH, Advantages
temperature, and the local composition bias of RNA), that - Mfold is very easy to use and free of charge online.
affect the RNA folding. Using thermodynamics in the - Mfold is internet based program that runs on
prediction algorithm of RNA structure is not common with (almost) any computer that has access to the
Single sequence secondary structure prediction software. Internet.
Up till now, only three programs, (Mfold, RNA fold, - Mfold has many versions and updated regularly.
RNAshapes), is known to use this feature (Table 1). Recently,
Mfold has been replaced by UNAFold, a software package
- The energetic model that Mfold uses ignores 3-D
that is much easier to install and run and it offers many more
interactions or protein-RNA interactions that could
types of computations.
stabilize a suboptimal fold.
Mfold History - Prediction from Mfold does not always correspond
SantaLucia (1998) have published his work on the unified to the true biological fold of the RNA. So that, the
view of polymer, dumbbell, and oligonucleotide DNA researcher should be able to make his own decision.
thermodynamics in PNAS journal. That paper was the base - The researcher should be able to judge the stability
for M. Zuker (1999) and his colleagues to study the expanded of the optimal fold when Mfold returns suboptimal
sequence dependence of thermodynamic parameters for the models.
prediction of RNA secondary Structure. Since then, Zuker - You cannot force pseudo-knots in Mfold.
has worked extensively to develop mfold, a program for - The time Mfold needs to analyze sequences
predicting the secondary structure of RNA and DNA, mainly increases very rapidly with their length.
by using thermodynamic methods, which was published at
Nucleic Acids Research journal in 2003 (Chain, 2005). Software Design
Mfold contribution to research Mfold can predict the energetically optimal secondary
Many researchers in the field of Molecular biology have structure of an RNA molecule by using of Zuker algorithm.
used using thermodynamics based Mfold modules during Versions of Mfold for Unix and Linux operating systems
their original research for predicting the secondary structure are available via a free license for academic and nonprofit
of RNA and DNA. With many citations in peer reviewed use only; commercial use is available for a fee.

*Corresponding author:
GERF Bulletin of Biosciences 2010, 1(1): 51-54 52

Name Description Links References

Secondary structure prediction based on generalized http://www.ncrna.or Hamada et al.
centroid estimator g/centroidfold/ (2009)
Secondary structure prediction method based on http://contra.stanfor Do CB et al.
conditional log-linear models (CLLMs), a flexible (2006.
CONTRAfold class of probabilistic models which generalize upon ver.html
feature- by using discriminative training and SCFGs
Secondary structure prediction method based on http://cylofold.abcc. Bindewald et al.,
CyloFold placement of helices allowing complex 2010
Folding kinetics of RNA sequences including http://kinefold.curie Xayaphoummin
KineFold pseudoknots by including an implementation of the .fr/cgi-bin/ e A, et al. 2005,
partition function for knots. 2003
http://frontend.bioin Zuker and Stiegler, 1981
Mfold MFE RNA structure prediction algorithm.
http://bibiserv.techf Reeder et al.,
A dynamic programming algorithm for the ak.uni- 2007
prediction of a restricted class of RNA pseudoknots.
http://rna.tbi.univie. Hofacker et al., 1994, McCaskill
bin/RNAfold.cgi 1990, Hofacker
MFE RNA structure prediction algorithm. Includes and Stadler
an implementation of the partition function for 2006,
computing basepair probabilities and circular RNA Bompfünewerer
folding. 2008)

MFE RNA structure prediction based on abstract http://bibiserv.techf Giegerich et

shapes. Shape abstraction retains adjacency and ak.uni- al.,2004, Voß et
nesting of structural features, but disregards helix al., 2006
lengths, thus reduces the number of suboptimal es/
solutions without losing significant information.
Furthermore, shapes represent classes of structures
for which probabilities based on Boltzmann-
weighted energies can be computed.
A program to predict lowest free energy structures http://rna.urmc.roch Mathews et al.
and base pair probabilities for RNA or DNA 2004,
sequences. Structure prediction can be constrained ture.html Mathews 2004
using experimental data, including SHAPE,
enzymatic cleavage, and chemical modification
accessibility. Graphical user interfaces are available
for Windows and for Mac OS-X/Linux. Programs
are also available for use with Unix-style text
interfaces. Additionally, a C++ class library is
http://sfold.wadswo Ding and
Statistical sampling of all possible structures. The Lawrence 2003,
Sfold sampling is weighted by partition function bin/ Ding et al. 2004,
probabilities. 2005, Chan et
al. 2005
Table: 1. Comparative table for other online for RNA Single sequence secondary structure prediction.
53 GERF Bulletin of Biosciences 2010, 1(1): 51-54

Limitation 7. Do CB, Woods DA and Batzoglou S (2006).

The current limit of the server is 3,000 bases. This is CONTRAfold: RNA secondary structure prediction
convenient for most non-coding RNAs except the largest without physics-based models. Bioinformatics 22
ribosomal ones (14): 90–8
Mfold availability online
8. Giegerich R, Voß Band Rehmsmeier M (2004).
Servers in USA: Abstract shapes of RNA. Nucleic Acids Res. 32
- (16): 4843–4851.
cgi-bin/rna-form1.cgi 9. Hofacker IL, Stadler PF (2006). Memory efficient
- folding algorithms for circular RNA secondary
structures. Bioinformatics 22 (10): 1172–6.
European mirrors of mfold:
- 10. Hofacker IL, Fontana W, Stadler PF, Bonhoeffer S,
mfold_submit Tacker M and Schuster P (1994). Fast Folding and
- Comparison of RNA Secondary Structures.
simple.html Monatshefte f. Chemie 125: 167–188.
Australian counterpart:
- 11. Markham NR and Zuker M (2008). UNAFold:
software for nucleic acid folding and hybridization.
References Methods Mol. Biol 453: 3–31.
1. Bindewald E, Kluth T and Shapiro BA (2010).
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CyloFold: secondary structure prediction including
(1999). Expanded Sequence Dependence of
pseudoknots. Nucleic Acids Research Suppl (W):
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lessons from Benasque. J Math Biol., 56 (1-2): 129–
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in base pairs predicted by free energy minimization.
3. Chan CY, Lawrence CE and Ding Y (2005). Structure RNA 10 (8): 1178–1190.
clustering features on the Sfold Web server.
14. Mathews DH, Disney MD, Childs JL, Schroeder SJ,
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Zuker M and Turner DH (2004). Incorporating
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of nucleic acids. Nucleic Acids Res. 32 (Web Server secondary structure, Proceedings of the National
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Complete probabilistic analysis of RNA shapes.
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Isambert H (2003). Prediction and statistics of
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