Nucleic Acids Research - Supplementary Material
[Description] [Source Code] [Run Instructions]The SlsDNADesigner generates sets of DNA/RNA strands that fulfill various combinations of combinatorial and thermodynamic constraints. The software was implemented in C & C++.
SlsDNADesigner uses the Pairfold library designed by Andronescu et al., 2002, 2003. Pairfold is available for download at: http://www.rnasoft.ca. Pairfold uses various sets of thermodynamic parameters for RNA [Turner Lab] and DNA [SantaLucia Lab] (not included here due to copyright issues). You can get access to DNA parameters if you ask directly Dr. John SantaLucia for permission.
The source code archive contains a precompiled version of the Pairfold library (compiled on Linux kernel 2.4.20-28.9smp), RNA parameters from Turner Lab, and a complete set of publicly available DNA parameters kindly provided by David Mathews.
| Parameter | Description |
| -len n | Word length n |
| -words k | Number of words k |
| -alph a | Alphabet size a (default: a=4) |
| -cutoff t | Maximum number of iterations t. The SLS algorithm is allowed to run for t iterations, after which it is interrupted and the result is displayed. |
| -tries tr | Number of consecutive independent re-runs of the SLS algorithm. |
| -randngb ngb | Size of the randomly generated neighborhood (ngb > 0). |
| -noise no | Probability of performing a random replacement versus a best improvement replacement (0 < no < 1, default: no = 0.2). |
| -temperature temp | Temperature of hybridization (default: temp=37 degrees Celsius). |
| -nucleicacid na | Nucleic acid: DNA or RNA (default: na=DNA). |
| -hd | Hamming Distance constraint threshold |
| -dist h | Hamming Distance threshold (0 <= h <= n). |
| -hdrc rc | Hamming Distance Reverse Complement threshold (0 <= rc <= n) |
| -gc | GC Content constraint |
| -gc_low gc_low | Minimum GC content |
| -gc_high gc_high | Maximum GC content |
| -fed | Word-Word Free Energy constraint |
| -fed_low fed_low | Minimum FED (fed_low <= 0) |
| -fed_high fed_high | Maximum FED (fed_low <= fed_high <= 0) |
| -fes | Perfect Match Free Energy constraint |
| -fes_low fes_low | Minimum FES (fes_low <= 0) |
| -fes_high fes_high | Maximum FES (fes_low <= fes_high <= 0) |
| -fer | Complement Mismatch Free Energy constraint |
| -fer_low fer_low | Minimum FER (fer_low <= 0) |
| -fer_high fer_high | Maximum FER (fer_low <= fer_high <= 0) |
| -fet | Complement-Complement Mismatch Free Energy constraint |
| -fet_low fet_low | Minimum FET (fet_low <= 0) |
| -fet_high fet_high | Maximum FET (fet_low <= fet_high <= 0) |
| -cms | Consecutive Mismatches constraint |
| -tm | Melting Temperature constraint |
| -tm_low tm_low | Minimum TM (0 <= tm_low) |
| -tm_high tm_high | Maximum TM (0 <= tm_low <= tm_high) |
| -cms_t cmst | Consecutive Mismatches threshold (0 <= cmst <= n) |
| -slides | Slide Mismatches constraint |
| -slides_t sldiest | Slide Mismatches threshold (0 <= slidest <= n) |
| -forbidden_substring fs | Forbidden Substring fs |
| -forbidden_substring_file fsf | Forbidden Substring File fsf |
| -fs_be fsbe | Forbidden Substring Begin-End fsbe |
| -show_results | Display Set of Words |
| -seed seed | Fix seed for pseudo-random number generator (helps to debug code and reproduce results) |
| -file fname | Initialize algorithm with words from file fname. |
| -conc_p conc_p | Concentration of words (used to compute TM) |
| -conc_t conc_t | Concentration of complements (used to compute TM) |
| -conc_s conc_s | Salt Concentration (used to compute TM) |
This sample run generates 10 (-words 10) RNA sequences of length 12 (-len 12), defined over an alphabet with 4 (-alph 4) letters (A,C,U,G). All RNA sequences have pair wise hamming distances (-hd) greater or equal with 6 (-dist 6). Each RNA sequence and its perfect complement have melting temperatures (-tm) in the range [30 .. 31] degrees Celsius. The stochastic local search algorithm is set to perform no more than 1000 iterations (-cutoff 1000) with a probabilistic noise of 0.1 (-noise 0.1).
Result:
begin trial 1
step 0: new best 3
step 1: new best 2
step 3: new best 1
step 4: new best 0
ACUCUCUUCUAA
AUAAUUGUAGAA
AUAAGUUAAUUG
CUCUUAGUAUUA
AAUUGUAAACUC
ACUGUUAUAAUA
ACUUAAUUUUUG
AUCUUGUAAAAC
GUAGUCUCUUUG
GAAAUAAAAUUA
Statistics:
==========
Accepted words = 410
Generated words = 102406
Acceptance rate = 0.400367%
end trial 1 (best solution = 0 after 4 steps)
Comments: Please let us know of any problems / bugs / questions / feedback / improvements that may arise from using our software. You can send your feedback at: dctulpan [at] cs [dot] ubc [dot] ca