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Finding Recurrent Motifs in RNA 3D Structures
Jesse Stombaugh
Bowling Green State University
RNA Society 2006
Outline“Find RNA 3D” (FR3D)
Geometric Search Screening Algorithm
Sample SearchSarcin Query MotifSarcin Search Results
Summary
Outline“Find RNA 3D” (FR3D)
Geometric Search Screening Algorithm
Sample SearchSarcin Query MotifSarcin Search Results
Summary
“Find RNA 3D” (FR3D) We have developed a suite of Matlab
programs, which allow for the search of RNA 3D structures.
Geometric search: given a query motif, find candidate motifs which are geometrically similar to the query motif, and rank them according to degree of similarity. (~ 2 min.)
Symbolic Search: Search for Candidates satisfying given basepairing and stacking constraints. (~ 5 sec.)
Combined search: geometric search with additional symbolic constraints. (~ 1 min.)
Outline“Find RNA 3D” (FR3D)
Geometric Search Screening Algorithm
Sample SearchSarcin Query MotifSarcin Search Results
Summary
Geometric Search
Consider a query motif (blue) and a candidate motif (red). Rigidly move candidate to align base centers (black dots). The fitting error L is the RMS sum of distances between
corresponding base centers. The orientation error A is the RMS sum of angles required to
rotate candidate bases onto query bases.
Geometric discrepancy ALmD
221
Geometric Search Discrepancies
In the 23S, there are 2754 bases. For a 4–nucleotide query motif, that makes
for: 2754 · 2753 · 2752 · 2751 = 5.7x1013 possible candidate motifs.
You cannot calculate the discrepancy for every conceivable candidate motif.
Instead, set a cutoff discrepancy D0 and find all candidates whose discrepancy with the query motif is smaller than D0.
Outline“Find RNA 3D” (FR3D)
Geometric Search Screening Algorithm
Sample SearchSarcin Query MotifSarcin Search Results
Summary
Screening Algorithm – Rejecting Candidates
(Q12-C12)2 ~ Large DiscrepancyMany candidates are nowhere close to the query motif.We derive the inequality:
where Qij is the distance between centers of bases i and j
in the query motif, and Cij for the candidate.
jili,j
ijijji
li i
CQwwwmD
211
Query Motif Candidate Motif
1
2
1
2
Screening Algorithm
Focusing on bases 1 and 2 in the query motif. Find all pairs in the structure whose distances are
similar.
Screening Algorithm
Focusing on bases 1, 2, and 3 in the query motif. Find all triples in the structure whose distances are
similar.
Screening Algorithm
Focusing on all in the query motif. Find all quadruples in the structure whose distances
are similar.
Outline“Find RNA 3D” (FR3D)
Geometric Search Screening Algorithm
Sample SearchSarcin Query MotifSarcin Search Results
Summary
Sarcin Query Motif
Basepairing
(Left) Identification of edges in the RNA bases. (Right) cis versus trans orientation of glycosidic bonds.
Sarcin Query Motif
Outline“Find RNA 3D” (FR3D)
Geometric Search Screening Algorithm
Sample SearchSarcin Query MotifSarcin Search Results
Summary
Sarcin Search Results
Local vs. Composite
Superposition of Local (black) and Composite (red, blue, cyan, green) Sarcin motifs
Local Sarcin motifFrom DI of 23S rRNA
Composite Sarcin motif from DII of 23S rRNA
Sarcin Search Results
Sarcin Search Results – Candidate 2
Sarcin Search Results – Candidate 3
Sarcin Search Results – Candidate 4
Sarcin Search Results – Candidate 5
Sarcin Search Results – Candidate 6
Sarcin Search Results – Candidate 7
Sarcin Search Results – Candidate 8
Outline“Find RNA 3D” (FR3D)
Geometric Search Screening Algorithm
Sample SearchSarcin Query MotifSarcin Search Results
Summary
Summary
We can find and rank motifs similar to a given query motif
We can apply symbolic constraints to narrow the search and reduce search time
The program FR3D is available at: http://rna.bgsu.edu/FR3D
Acknowledgements
Organizers of the RNA Society
BGSU – ChemistryNeocles Leontis, P.I.Ali Mokdad (Poster #215)Lorena NasaleanKirill Afonin
BGSU – Math. And Stats. Craig ZirbelMike Sarver