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Fold is used to predict the lowest free energy structure and a
set of suboptimal structures, i.e. low free energy structures,
using a variety of constraints. Fold-smp is a parallel
processing version for use on multi-core computers, built using
OpenMP.
USAGE: Fold <seq file> <ct file> [options]
OR: Fold-smp <seq file> <ct file> [options]
| <seq file> |
The name of a sequence
file containing input data.
Note that lowercase nucleotides are forced single-stranded
in structure prediction. |
| <ct file> |
The name of a CT file
to which output will be written. |
| -d, -D, --DNA |
Specify that the sequence is DNA, and DNA parameters
are to be used.
Default is to use RNA parameters. |
| -h, -H, --help |
Display the usage details message. |
| -a, -A, --alphabet |
Specify the name of a folding alphabet and associated
nearest neighbor parameters. The alphabet is the prefix
for the thermodynamic parameter files, e.g. "rna" for RNA
parameters or "dna" for DNA parameters or a custom
extended/modified alphabet. The thermodynamic parameters
need to reside in the at the location indicated by
environment variable DATAPATH.
The default is "rna" (i.e. use RNA parameters). This
option overrides the --DNA flag. |
| -c, -C, --constraint |
Specify a folding
constraints file to be applied. For Fold, current
supported constraints are force pairs, force a nucleotide
to be single stranded, and force a nucleotide to be double
stranded.
Default is to have no constraints applied.
Note: Constraints should be added with caution. The current folding algorithm does not allow base pairs that cannot stack on adjacent pairs. So constraining a pair effectively also requires that at least one adjacent pair can be formed. |
| -dms, -DMS, --DMS |
Specify a file with normalized DMS reactivity data.
These data will be applied as a pseudoenergy restraint.
The data are specified in a file using the SHAPE
data file format. |
| -dsh, -DSH, --DSHAPE |
Specify a differential SHAPE
data file to be used to generate restraints in
addition to SHAPE restraints specified by --SHAPE. These
restraints specifically use SHAPE pseudoenergy restraints
where the offset is zero. Also, the function for
calculating the pseudo free energy for nucleotide i is =
(differential slope) * (differential SHAPE for nucleotide
i). These pseudoenergies are added to those generated with
the --SHAPE option.
Default is no differential SHAPE data file specified. |
| -dsm, -DSM, --DSHAPEslope |
Specify a slope used with differential SHAPE restraints.
Default is 2.11 kcal/mol. |
| -dso, -DSO, --doubleOffset |
Specify a double-stranded offset
file, which adds energy bonuses to particular
double-stranded nucleotides.
Default is to have no double-stranded offset specified. |
| -l, -L, --loop |
Specify the maximum number of unpaired nucleotides in
an internal or bulge loop.
Default is 30 unpaired nucleotides.
|
| -m, -M, --maximum |
Specify a maximum number of structures. Note that
suboptimal structures are generated until either the
maximum number of structures are reached or the maximum
percent difference is reached (below).
Default is 20 structures. |
| -md, -MD, --maxdistance |
Specify a maximum pairing distance; that is, the
maximum number of bases between the two nucleotides in a
pair.
Default is no restriction on the distance between pairs. |
| -mfe, -MFE, --MFE |
Specify that only the minimum free energy structure
should be generated. This saves about half the computation
time, but provides less information. The -p and -m options
are ignored. Also, no save files can be generated using
-s.
|
| -p, -P, --percent |
Specify a maximum percent difference in folding free
energy change for generating suboptimal structures. For
example, 20 would indicate 20%.
Default is determined by the length of the sequence. |
| -s, -S, --save |
Specify the name of a save file, needed for dot plots
and refolding.
Default is not to generate a save file. |
| -sh, -SH, --SHAPE |
Specify a SHAPE data
file to be used to generate restraints. These
restraints specifically use SHAPE pseudoenergy restraints.
Default is no SHAPE data file specified. |
| -si, -SI, --SHAPEintercept |
Specify an intercept used with SHAPE restraints.
Default is -0.6 kcal/mol. |
| -sm, -SM, --SHAPEslope |
Specify a slope used with SHAPE restraints.
Default is 1.8 kcal/mol. |
| -sso, -SSO, --singleOffset |
Specify a single-stranded offset
file, which adds energy bonuses to particular
single-stranded nucleotides.
Default is to have no single-stranded offset specified. |
| -t, -T, --temperature |
Specify the temperature at which calculation takes
place in Kelvin.
Default is 310.15 K, which is 37 degrees C. |
| -usi, -USI, --unpairedSHAPEintercept |
Specify an intercept used with single-stranded SHAPE
constraints.
Default is 0 kcal/mol. |
| -usm, -USM, --unpairedSHAPEslope |
Specify a slope used with single-stranded SHAPE
constraints.
Default is 0 kcal/mol. |
| -w, -W, --window |
Specify a window size.
Default is determined by the length of the sequence. |
| -x, -X, --experimentalPairBonus |
Specify a text
file with a two-dimensional matrix of bonuses (in
kcal/mol) to apply to each residue pair, as might be
obtained from a mutate/map measurement. The matrix must
have the same number of rows and columns as the target
RNA. Bonus is applied once to edge base pairs, twice to
internal base pairs.
Default is no experimental pair bonus file specified. |
| -xo |
Specify an intercept (overall offset) to use with the
2D experimental pair bonus file.
Default is 0.0 (no change to input bonuses). |
| -xs |
Specify a number to multiply the 2D experimental pair
bonus matrix.
Default is 1.0 (no change to input bonuses). |
- The
first approach, explained in reference 3, is better when the DMS
data are analyzed qualitatively. In this approach, the
DMS-reactive nucleotides are specified as nucleotides accessible
to chemical modification in a constraint
file. The constraint file is then read using the -c
option.
- The second approach is better when the DMS
reactivities are quantified. This approach requires
specification of normalized reactvities, using a
SHAPE data file format. This file is then read using the
-dms option. This approach is explained in reference 5.
Fold-smp, by default, will use all available compute cores for
processing. The number of cores used can be controlled by
setting the OMP_NUM_THREADS environment variable.
- Reuter, J.S. and Mathews, D.H.
"RNAstructure: software for RNA secondary structure prediction
and analysis."
BMC Bioinformatics, 11:129. (2010).
- Deigan, K.E., Li, T.W., Mathews, D.H.
and Weeks, K.M.
"Accurate SHAPE-directed RNA structure determination."
Proc. Natl. Acad. Sci. U.S.A., 106:97-102. (2009).
- Mathews, D.H., Disney, M.D., Childs,
J.L., Schroeder, S.J., Zuker, M. and Turner, D.H.
"Incorporating chemical modification constraints into a
dynamic programming algorithm for prediction of RNA secondary
structure."
Proc. Natl. Acad. Sci. USA, 101:7287-7292. (2004).
- Mathews, D.H., Sabina, J., Zuker, M.
and Turner, D.H.
"Expanded sequence dependence of thermodynamic parameters
provides improved prediction of RNA secondary structure."
J. Mol. Biol., 288:911-940. (1999).
- Cordero, P., Kladwang, W., VanLang,
C.C., and Das, R.
"Quantitative dimethyl sulfate mapping for automated RNA
secondary structure inference."
Biochemistry, 51: 7037-7039. (2012).
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