III SIMPÓSIO INTERDISCIPLINAR FÍSICA +
BIOINFORMÁTICA
22 A 25 DE ABRIL DE 2014
UNIVERSIDADE FEDERAL DE UBERLÂNDIA, UBERLÂNDIA, MINAS GERAIS
Investigation of GU mismatch stability and parameters from melting
temperatures by a mesoscopic model
Tauanne D Amarante* (PG), Rodolfo V Maximiano (PG), Gerald Weber (PQ)
Universidade Federal de Minas Gerais - Instituto de Ciências Exatas - Departamento de Física, Av. Antônio Carlos,
6627, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil, Tel 55-31-3409-5633 Fax 55-31-3409-5600
e-mail: tauamarante@gmail.com
Keywords: RNA structure, Peyrard-Bishop model, Hydrogen bonding, stacking.
INTRODUCTION
The mismatch GU is the most common base pair
besides Watson-Crick in RNA. Due to this
prevalence, it is essential to study GU base pairs to
understand the secondary structure of RNA. In the
wobble hypothesis, Crick proposed that GU could
form two hydrogen bonds similar to the canonical
AU pair.
It was already discovered that this motif plays an
important role for recognition of some biomolecules.
There are experimental evidences that the stability
of internal GU mismatches depends on the neighbor
context. Also, if a GU base pair is followed by
another GU mismatch in tandem, the way they are
arranged strongly affects the thermodynamic
stability: 5'-UG-3' is more stable than 5'-GU-3'. NMR
experiments of some sequences show that the
symmetric tandem GU base pair may have either
one or two hydrogen bonds.
METHODS
We study the GU mismatch with a mesoscopic
model [1], using the method developed by Weber et
al. [2,3] to obtain the model parameters. With this
technique it is possible to investigate the hydrogen
bonds and stacking interaction of GU from melting
temperatures. The set of experimental data was
obtained from [4].
RESULTS AND DISCUSSION
To take into account the context of the GU
mismatch, we introduce a context dependent Morse
parameter D. We then perform the minimization
procedure and analyze the resulting Morse potential
which allowed us to estimate the amount of
hydrogen bonding for the specific GU context.
In our preliminary results allowing 5'-GU-3' to be
distinguishable from 5'-UG-3', we observed that the
value obtained for the parameter D of the Morse
potential is larger for 5'-UG-3' (see table 1). This
result is in agreement with the experiments which
indicate that except for 5′GGUC/3′CUGG, the
5′UG/3′GU motif is more stable than 5′GU/3′UG.
For most of the GU internal mismatches the
predicted value for Morse D is smaller and close to
the predicted value for AU, as expected according to
some experiments[4].
Table 1. Morse parameter D for GU mismatches in
different contexts. The underline refers to terminal
pairs.
GU mismatches grouped by similar contexts
D (eV)
AGA/UUU ; AGU/UUA; AUA/UGU; UGA/AUU
0.026
AGC/UUG;AGG/UUC; AUC/UGG; AUG/UGC; 0.038
CGA/GUU; CUA/GGU; GGA/CUU; GUA/CGU
AGG/UUU; AUU/UGG; GGA/UUU; UGG/AUU 0.004
AGU/UUG;GUA/UGU
0.002
AG_/UU_;AU_/UG_;UG_/AU_; UU_/AG_
0.057
AUG/UGU; UGA/GUU
0.032
CGC/GUG;CGG/GUC;CUC/GGG; GGC/CUG 0.034
CGG/GUU;CUU/GGG;GGC/UUG; GGG/CUU 0.036
CGU/GUG;GGU/CUG
0.019
CG_/GU_;CU_/GG_;GU_/CG_; GG_/CU_
0.052
CUG/GGU;GUG/CGU
0.040
CONCLUSIONS
Using a mesoscopic model to study the GU
mismatch, we were able to estimate both the
hydrogen bonds and the stacking parameters. Our
results agree with the experimental measurements.
ACKNOWLEDGMENTS
CNPq, Capes, Fapemig and INCT for Complex System
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[1]Peyrard M and Bishop A R 1989 Phys. Rev. Lett. 62 2755-2757
[2] Weber G, Haslam N, Whiteford N, Prügel-Bennett A, Essex J W and
Neylon C 2006 Nature Physics 2 55-59
[3] Weber G, Essex J W and Neylon C 2009 Nature Physics 5 769-773
[4]Chen, J. L., Dishler, A. L., Kennedy, S. D., Yildirim, I., Liu, B.,
Turner, D. H., & Serra, M. J. 2012. Biochemistry, 51(16), 3508-3522.