RNA Secondary Structure Prediction

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• RNA Secondary Structure Prediction

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(No Transcript)
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16s rRNA
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RNA Secondary Structure
Pseudoknot
Dangling end
Single- Stranded
Interior Loop
Junction (Multiloop)
Bulge
Stem
Hairpin loop
Image Wuchty
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RNA secondary structure
G A A A G G
A-U U-G C-G A-U
G-C
Loop
wobble pair
Stem
canonical pair
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RNA secondary structure representation
Legitimate structure
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Non-canonical interactions of RNA
secondary-structure elements
These patterns are excluded from the prediction
schemes as their computation is too intensive.
Pseudoknot
Kissing hairpins
Hairpin-bulge contact
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Rules for 2D RNA prediction

• Base Pairs in stems GOOD
• Additional possible assumptions e.g., GC better
  than AT
• Bulges, Loops BAD
• Canonical Interactions (base pairs, stems,
  bulges, loops) OK
• Non canonical interactions (pseudoknots, kissing
  hairpins) Forbidden
• The more interactions The better

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Predicting RNA secondary Structure

• Allowed base pairing rules (Watson-Crick AU,
  GC, and Wobble pair GU)
• Sequences may form different structures
• An free energy value is associated with each
  possible structure
• Predict the structure with the minimal free
  energy (MFE)

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Simplifying Assumptions for Structure Prediction

• RNA folds into one minimum free-energy structure.
  
• There are no non-canonical interactions (base
  pairs never cross).
• The energy of a particular base pair in a double
  stranded regions is sequence independent
• Neighbors do not influence the energy.

Was solved by dynamic programming Zucker and
Steigler 1981
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Sequence-dependent free-energy (the nearest
neighbor model)
U U C G U A A
U G C A UCGAC 3
U U C G G C A
U G C A UCGAC 3
Example values GC GC GC GC AU GC
CG UA -2.3 -2.9 -3.4 -2.1
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Free energy computation
U U A A G C
G C A G C U A A U
C G A U A 3 A 5
5.9 (4 nt loop)
-1.1 mismatch of hairpin
-2.9 stacking
3.3 (1 nt bulge)
-2.9 stacking
-1.8 stacking
-0.9 stacking
-1.8 stacking
5 dangling
-2.1 stacking
-0.3
G -4.6 KCAL/MOL
-0.3
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Prediction Programs

• Mfold
• http//www.bioinfo.rpi.edu/applications/mfold/old/
  rna/form1.cgi
• Vienna RNA Secondary Structure Prediction
• http//rna.tbi.univie.ac.at/cgi-bin/RNAfold.cgi

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Mfold - Suboptimal Folding

• For any sequence of N nucleotides, the expected
  number of structures is greater than 1.8N
• A sequence of 100 nucleotides has 3?1025
  possible folds. If a computer can calculate 1000
  folds/second, it would take 1015 years (age of
  universe 1010 years)!
• Mfold generates suboptimal folds whose free
  energy fall within a certain range of values.
  Many of these structures are different in trivial
  ways. These suboptimal folds can still be useful
  for designing experiments.

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Example
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Output