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Sequential Folding ModelSequential Folding Modelpredicts length-independent secondary structure
properties of RNAs
Li Tai Fang
RNA
a biopolymer consisting of 4 different species of monomers (bases): G, C, A, U
GAG
secondarystructure
–––
CUU
Sequential Folding Model
Very simple Predicts generic secondary structure properties
of RNA Pairing fraction Duplex length Loop size Maximum ladder distance (MLD) → 3D size
Maximum Ladder Distance (MLD)
Approximating RNA into a linear polymer
The longest stretch determines its 3D size
MLD is a measure of 3D size: Rg ~ MLD1/2
Sequential Folding Model (SFM)
Created by A. Ben-Shaul
In each generation: find the longest duplex
Analytical solution
GAG
CUU
–––
Matching probability = 3/8
P(k) = (3/8)k
For k << NNumber of alignments of length k = (1/2)N2
On average, the longest duplex is determined by:(3/8)k1 (1/2)N2 = 1
k1 = a ln N – b, a = 2 / ln (8/3) ; b = ln 2 / ln (8/3)
CUU
k = duplex length
Average Duplex Length: Assumptions:
All divisions are symmetrical k << loop size in all generations (no longer valid
toward the end of the successive foldings)− Loop size in the sth generation of division: N
s = N / 2s
− ks = k
1 – (a ln 2)(s – 1)
s^ = the final generation k
s^ = 2, because 2 is the shortest stable duplex
ks^ + a ln 2
Pairing fraction: f
D = # of duplex; L = # of loops;
<k> = <duplex length>; <l> = <loop size>
D = L
D = N۰f / 2<k> ; L = N۰(1 – f) / <l>
f = 2 <k> / (<l> + 2<k>)
Assuming ks^ ~ 2 → <l> ~ 4
f ~ 0.68
Numeric results:predicted secondary structures
A) Vienna RNA B) SFM
Pairing fraction
Fang et. al., J. Phy. Chem. B (2011)
Duplex length
Fang et. al., J. Phy. Chem. B (2011)
Maximum ladder distance
Slope ~ 0.7
Fang et. al., J. Phy. Chem. B (2011)
Current Work: Kramer's theorem: mapping RNA secondary structure into
an “ideal” branched polymer
Acknowledgement:
– Avi Ben-Shaul: conceptualized the model
– Bill Gelbart
– Aron Yoffe