volume 8 Number 171980
N u c l e i c A c i d s Research
Role of interaction energy in the specificity of transcription. II- The Watson Crick A-U base
pair template
Nitish K.Sanyal, U.Kumar and Mihir Roychoudhury
Department of Physics, University of Gorakhpur, Gorakhpur 273001, India
Received 27 May 1980
ABSTRACT
In c o n t i n u a t i o n with work regarding the e v a l u a t i o n of the
energy of a s s o c i a t i o n of various BNA bases with various base
pairs, the results of the computations of the electrostatic Interaction energy of A-U base pair with four RHA bases viz. Adenine,
Uracil Guanine and Cytosine have been reported. Non bonded
Induced polarization and dispersion potentials are not taken into
account. Electrostatic hard sphere model of Nash and fradley has
been employed. Computations have been performed to find out the
minimum energy configuration out of the various possible complex
configurations. Results have been discussed with reference to
similar calculations with G-C base pair performed by the authors.
IHTRODPCTIOH
In our e a r l i e r s t u d i e s 1 ' 2 ' 3 i t was observed that (1) t h e
e l e c t r o s t a t i c i n t e r a c t i o n energy between the base-pairs and the
RHA bases offer a high specificity of selection in the transcription process and (11) the Watson-Crick Guanine-Cytosine base pair
in the ISA double helix can behave as a double code viz. (a) G-C
(b) C-G, Guanine or Cytosine are attached to the system according
to the i n i t i a l side of the RNA strand formation.
Hence, i t becomes necessary to extend similar studies with
Adenine-Thymine or similar set of base pairs and examine their
characteristic behaviour in such transcription process. In this
paper, we report the results of our investigations with AdenlneDracil base pair. The results are also applicable for AdenineThymlne base pair since the structure and charge distribution in
this case i s also similar (except for the methyl group at the C6
position in Thymine Instead of hydrogen In Uracil).
The details of the methods of computations are exactly siml(DIRL Press Limited. 1 Falconberg Court London W1V5FG, U.K.
3983
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Nucleic Acids Research
lar to that given in the earlier paper of this series.
BBSPI3B AND DIBCPSfilOHS
The energy values obtained for different base coaplexes with
A-U base pair are given In Table 1. The related curves are also
shown In Fig. 2. The figures I-XII In Fig. 1 shown the schemat i c representation of the base pair-base complexes at the minimum energy configuration.
(a) Interaction Baergies
Interaction energies corresponding to a l l the four bases
are attractive only for a limited region of space. Thus, the
energy value varies from -£ E Cal/3 soles to + 2 K Cal/3 moles
of base while translating the base throughout the available space
inside the deep groove of the double helix. In other words, for
different bases (normal and 180° rotated along the glycosldic
bond), there are different specific binding s i t e s in the region
around the base pair where association may take place.
(b) Minimum Biergy Configuration
I t i s not possible to classify the bases in A-U or A-T
system on the basis of their preference to association, as was
possible In the case of G-C base pair, because the minimum
energy values for a l l the bases l i e in a relatively small range
(between -0.5 K Cal/3 mole t o -2.0 K Cal/3 mole).
From the above observations, i t appears that A-U base pair
has no s p e c i f i c i t y for the selection of a RNA base. Actually
t h i s may be true for an Independent base pair residing in a cocrystal or in solution or elsewhere. However, in a QNA double
helix, on which RNA transcription has already been initiated,
random association cannot allow the formation of a m-RNA sugar
backbone. In these cases, the sum t o t a l of the base pair-base
interaction energy and the backbone distortion energy becomes
important to have the necessary specificity condition. In our
considerations, the backbone distortion energy has not been
evaluated e x p l i c i t l y . An alternative procedure has been adopted
which Is as follows: It has been assumed that In the environment
of DNA, the relative abundances of the nucleotides are large. The
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iznr
sir
Figure 1
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-6
-2
+2
+6
Figure 2
magnitude of the Interaction energy of G (or C) with G-C pair Is
much larger than that of all other M A base-G-C pair and RNA base
-A-D pair Interactions, Indicates the high specificity of association of G-C pair. In order to form a stable super helix of m-RNA,
the site of A-U pair-RNA base association will be conditioned by
the specific G-C pair association, so that the backbone distortion is minimum. Thus supposing all the G-C pairs in the transcription region of the DMA, as already been attached by ooae base
forming a single strand, one can assign a hypothetical sugar end
point for the base associating with the A-D pair so that there is
no distortion in the backbone of the super helix. The distortion
energies of the bases joining the A-U pair can be correlated with
the distance of the sugar end of the third base from the hypothetical sugar end point already specified by the G-C base pair.
Obviously, the distortion energy will be a positive quantity and
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Its magnitude will be directly proportional to the aforesaid
distance. Hence, if a trimar configuration having the sugar end
of the third base at a minimum distance from the hypothetical
sugar end of M - H N A chains having orientation almost identical to
the orientation fixed by G-C pair is selected, it can safely be
said that the natural selection has been tra ced without going
through the detailed backbone distortion energy calculations.
The conclusion has been drawn with the help of the Pig.(3).
The various arrows represent the sugar contact points (the bond
between ribose and nitrogen base) of the third bases in the mlnlmum energy configurations. The head of the arrows point towards
the ribose while the tail touches the nitrogen atoms of the bases
at the sugar end (S9 for Purine and Nl for Pyrlmidine). The
arrows, therefore, simultaneously represent the positions and the
orientations of the various bases. The starred (solid and dashed)
arrows represent the hypothetical sugar end points fixed by the
C-G and G-C pairs respectively.
• 6
-1.38
\
, \
A
ID
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VI
-4
-2
0
+2
+4
+6
+8
Figure 3
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COHCLOSIOg
An observation of t h e P i g . 3 Immediately suggests that the
A-U pair a l s o s e r v e s as a double code, one as A-U and the other
a s U-A with a r e l a t i v e l y low i n t e r a c t i o n energy. They link U r a c i l
or Adenlne depending on the i n i t i a l s e l e c t i o n of the binding s i t e .
Thus, t h e s t r u c t u r e s I and 7 with I n t e r a c t i o n energies - 0 . 1 6 and
- 1 . 6 7 r e s p e c t i v e l y g i v e the c o n f i g u r a t i o n s a p p l i c a b l e for RNA
t r a n s c r i p t i o n process through t h e s e energy c o n s i d e r a t i o n s . I t i s
i n t e r e s t i n g t o note that these are i n agreement v i t h Stent's
scheme of BNA t r a n s c r i p t i o n 4 from the s t r u c t u r a l point of v l e v
they correspond t o aibays model 'B'*"®.
Consideration of t r a n s c r i p t i o n s p e c i f i c i t y as a base-base
pair I n t e r a c t i o n problem leads t o some important c o n c l u s i o n s . I t
w i l l be discussed i n t h e sane sequence ve r a i s e d the questions
against t h e enzymatic mechanism i n the 1 s t paper of t h i s s e r i e s .
(1) s i n c e t h e r e i s no need t o presume the opening of t h e DNA
strands, t h e question of synthesis of two strands does not a r i s e ,
( i i ) By a c t u a l computation, we have shown t h a t (A-T)U i n t e r a c t i o n
energy i s much larger than that of ( A - T ) T 7 . The absence of Thymine
i n BNA i s automatically e x p l a i n e d ^ ( i l l ) As the phosphrous atoms
are highly polar, the preferred s i t e of electrostatic interaction
i s near the phosphorous atom in DNA. The presence of cations
(counterions), due to their larger mobility interact with them
earlier and make the deep groove more preferred for the RNA bases.
In addition to these, the observation of the helix centre to sugar
end distances of the proposed trliners suitable for transcription
show that they are much shorter than the stable DNA helix radius.
Thus i t can be inferred that after the formation of the backbone,
when cooperative stacking forces play their part, the nevly formed
RNA chain has a tendency to separate from the DNA and consequently
the RNA i s released. Such studies alongwith the studies vith i n i t i ation and termination code seem3 to be interesting and results
w i l l be published in due course soon.
ACKWOWLEDGBtBfr
One of us (MRC) i s thankful t o NCERT, I n d i a f o r f i n a n c i a l
a s s i s t a n c e i n t h e form o f NSTS s c h o l a r s h i p f o r p r e d o c t o r a l work.
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REFERiMCBS
1. Sanyal, N.K., Kumar, U and Slnha, R.P. (1977) J.Thoor.Blol.
66, 3 9 U 6 .
Sanyal, N.K., Kumar, U and Boychoudhury, M. (1978) J.Theor.
2 . Sanyal.
B l o l . (communicated).
3 . Sanyal, N.K., Ktanar, U and Boychoudhory, M. (1978). In 'Assoc i a t i o n of a Watson-Crick base pair with a RHA base i n BNA
t r a n s c r i p t i o n ' . Paper presented a t the I n t e r n a t i o n a l Symposium
on Bionolecular structure, conformation, function and evolution
Madras, India.
4.
6.
6.
7.
Lovdln, P.O. (1964) Adv. Quant. Chem. £ , 213-304.
aibay, G. (1958) Nature 182, 1UB-113.
3ibay, G. (1958) Nature 182, 1290-1292.
Sanyal, N.K., Kumar, D. and Boychoudhury, M. (1978). Natl.
Acad. S c l . Letters ( I n d i a ) , September i s s u e , p.
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