Technical report TR No: IIIT-H/TR/2004/011.
Theoretical Studies of non-Watson-Crick Base Pairs in Double Helical Regions
of Different RNA Structures
Bhabdyuti Sinha1, Dhananjay Bhattacharyya2, Abhijit Mitra1
Abstract: Mismatch base pairs are suggested to play an important role in the stabilities of RNA structures, and
may provide important clues for 3D-structure prediction. In the present paper we report our approach towards
the generation of a database of the occurrence density along with structural classification and corresponding
calculated stabilities for non-Watson-Crick base pairs in functional RNA structures. We have used available xray data to analyze the stabilities of all such base pairings involving anti-parallel strand orientation and all types
of edge interactions using the MOROKUMA method and BSSE provided in GAMESS-US package, for the
calculation of interaction energy. Our calculations show that G-U, A-G, A-C, A-A, G-G and C-C pairings lead
to substantial stabilization.
1
Bioinformatics Research Center, International Institute of Information Technology, Hyderabad - 500 019
2
Biophysics Division, Saha Institute of Nuclear Physics, Calcutta -700 037
Introduction: Non-Watson-Crick base-pairs are now widely observed in functional RNA
structures determined experimentally1. Leontis2 et al have proposed that bases interact using
any one of three edges and have classified base-pair interaction according to the orientation
of the glycosidic bonds and the chemical faces participating in H-bonding interaction.
Recently Malathi3 et al have indicated the role of non-Watson-crick base pairs in stabilizing
functionally important RNA structural motifs in ribozymes. In this investigation we have
studied base-pairing using 3DNA4 software and have performed a statistical analysis of the
frequency distribution of diverse of interactions in the RNA structure database
(http://www.rnabase.org). In order to investigate the energy related significance of such nonWC base-pairs we have carried out ab initio quantum chemical calculations with typical
individual cases. For comparing, we present the molecular interaction energies obtained at
the experimental geometries as well as at fully optimized geometries with BSSE-correction
invoked in both cases.
Methods: We have used GAMESS-US5 for partial and full optimizations of the geometries at
the HF/6-31G** level and MOROKUMA6 method for BSSE correction. We have used
MOLDEN7 for visualization and preparing input files.
Figure 1. (Left) Identification of edges in the RNA bases. (Right) cis versus trans orientation of glycosidic
bonds.(Reproduced from reference 6)
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Technical report TR No: IIIT-H/TR/2004/011.
Non Watson-Crick base pairs are often found in RNA structures. Occurrence frequency of
such unusual base pairs is quite comparable with that of the usual W-C types.
G:C
A:U
G:U
G:A
G:G
U:C
A:A
A:C
C:C
U:U
Number of Occurrence (and percentage) Occurrences of Unusual Base Pairs
of different types of Base Pairs in RNA within Double Helical Regions in
Structures
RNA
9465 (50.25%)
34
3290 (17.47%)
10
1393 (7.39%)
67
577 (3.06%)
25
241 (1.28%)
6
(< 0.5%)
6
364 (1.94%)
5
(< 0.5%)
5
157 (0.83%)
2
297 (1.58%)
2
Non Watson-Crick base pairs are often seen well within double helical regions of functional
RNA crystal structures. A typical example of a G:A base pair in double helical RNA (NDB
ID: RR0064) is shown below.
Fully Optimized Structures (HF/6-31G**) of Cis WC/WC base pairs.
A19-U14 AR0006
ΔE-BSSE = -10.42 Kcal/mol
C1’-C1’distance = 10.13 (Å)
G4-C21 URL050
ΔE-BSSE = -25.49 Kcal/mol
C1’-C1’distance = 10.20 (Å)
G215-A105 URX053
ΔE-BSSE = -12.77 Kcal/mol
C1’-C1’distance = 12.37 (Å)
A1912-A1927 RR0033
ΔE-BSSE = -4.21Kcal/mol
C1’-C1’ distance = 12.17 (Å)
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Technical report TR No: IIIT-H/TR/2004/011.
Fully Optimized Structures (HF/6-31G**) of Trans WC/Hoogsteen base pairs.
U103-A73 URL064
ΔE-BSSE = -10.86 Kcal/mol
C1’-C 1’ distance= 8.88 (Å)
A7-A6 URL051
ΔE-BSSE = -8.03 Kcal/mol
C1’-C1’ distance = 11.56 (Å)
C163-A148 PR0021
ΔE-BSSE = -11.36 Kcal/mol
C1’-C1’ distance = 10.26 (Å)
G2082-G535 RR0033
ΔE-BSSE = -16.70 Kcal/mol
C1’-C1’ distance = 10.34 (Å)
Fully Optimized Structures (HF/6-31G**) of (a) Cis WC/WC, (b) and (c) Trans
WC/Hoogsteen and (d) Cis WC/Sugar Edge GU base pairs.
G9-U20 AR0008
ΔE-BSSE = -13.26 Kcal/mol
C1’-C1’ distance = 9.94 (Å)
G188-U168 URX053
ΔE-BSSE = -12.84 Kcal/mol
C1’-C1’ distance = 11.67 (Å)
U2419-G2404 RR0033
ΔE-BSSE = -6.56 Kcal/mol
C1’-C1’ distance = 8.98 (Å)
U1435-G1389 RR0033
ΔE-BSSE = -15.15 Kcal/mol
C1’-C1’ distance = 4.57 (Å)
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Technical report TR No: IIIT-H/TR/2004/011.
Fully Optimized Structures (HF/6-31G**) of Trans WC/Hoogsteen (a) C-C and (b) U-U and
Hoogsteen/Sugar Edge (c) U-G and Cis Hoogsteen/Hoogsteen (d) G-A.
C1834-C1841 RR0033
ΔE-BSSE = -9.09 Kcal/mol
C1’-C1’ distance = 9.38 (Å)
U1-U2 URF042
ΔE-BSSE = -6.77 Kcal/mol
C1’-C1’ distance = 10.56 (Å)
G531-U12 RR0033
ΔE-BSSE = -15.15 Kcal/mol
C1’-C1’ distance = 4.57 (Å)
A1742-G2033 RR0033
ΔE-BSSE = -6.39 Kcal/mol
C1’-C1’ distance = 9.94 (Å)
Conclusions: The results of calculation of molecular interaction energy of non-Watson-Crick
base pairs by MOROKUMA method are quite satisfactory when compared to other
theoretical calculations8-9. The non-complementary base-pairing G-U, A-G, A-C, AA, GG
and CC are stabilizing enough to play significant role in functional RNA structures.
References
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(2002).
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