Density Functional Theory Studies on Guanine and Cytosine

W. N. Zaharim

, S. Sulaiman

1,2

, S. N. Abu Bakar

, N. E. Ismail

, H. Rozak

1,3

and I. Watanabe

1,3

Computational Chemistry and Physics Laboratory, School of Distance Education, Universiti Sains Malaysia, Pulau

Pinang 11800, Malaysia.

USM-RIKEN International Center for Ageing Science, School of Distance Education, Universiti Sains Malaysia, Pulau

Pinang 11800, Malaysia.

Advanced Meson Science Laboratory, RIKEN Nishina Center, Wako, Saitama 351-0198, Japan

nureliana_ismail@yahoo.com, harisonrozak7@gmail.com

Keywords: DNA, electron transport, Density Functional Theory, electronic structure.

Abstract: DFT cluster method was employed to investigate the electronic structures of guanine and cytosine in the

form of nucleobase and nucleotide. All calculations were performed at the B3LYP/6-311++G (d,p) level.

From the computational study, the presence of methyl group or sugar phosphate group to the nucleic acid

bases has a direct effect on the structure of the system. The planar structure of the nitrogenous base is

maintained after geometry optimization procedure. No significant difference was found in the charge

distribution in nucleobase and nucleotide for both guanine and cytosine. The ionization energy for guanine

is found to be lower than that for cytosine. The HOMO-LUMO gap is lower for both guanine and cytosine

in the nucleobase form. The calculated dipole moment shows that guanine is more polarized than cytosine.

1 INTRODUCTION

Deoxyribonucleic acid (DNA) is a versatile

molecule that stores genetic information and consists

of two polynucleotide chains twisted around each

other in the form of a double helix. DNA is formed

using sequences of four nitrogenous bases. These

four bases are guanine (G), adenine (A), cytosine

two groups. Guanine and adenine belong to the

purine group which is considered as a good electron

donor. Cytosine and thymine on the other hand

belong to the pyrimidine group which is poor

electron donor as compared to the purine group.

Purines and pyrimidines are considered as aromatic

compounds and are electron rich in nature (Garrett

and Grisham, 2002). The molecular formulas for

adenine, guanine, cytosine and thymine bases are

, C

O, C

O, and C

respectively (Kim et al. 2015). In double strand

DNA, the four bases are arranged in a pair by

forming hydrogen bond between the bases. Adenine

on one strand will pair up with thymine base on the

other strand, while guanine pair up with cytosine.

These nitrogenous bases will be ordered in some

ways to provide the necessary information to make

proteins for building and maintaining an organism.

All four nitrogenous bases have different electronic

structure and chemical structure. The molecular

orbital and electron distribution for all nitrogenous

bases are different from one another.

DNA bases are considered as an organic

molecular compound that has the ability to transport

electron through (Chakraborty, 2007). In general,

electron transport occurs in many important

biological processes such as the storage and

consumption of energy, enzyme response, and DNA

UV damage repair (Klotsa et al. 2005). Electron

transport along the DNA molecule and the potential

application of DNA molecule has caught the

attention of many chemists and physicists. DNA is a

biological molecule that has potential in fabrication

and construction of electronic nanodevices due to

their electronic properties (Cai et al. 2000 and Kaur

et al. 2011). Studies using varieties of experimental

approaches show that DNA is an effective medium

for charge migration (Apalkov et al. 2007). To study

the electron transport or charge migration through

DNA, the electronic structure of DNA bases need to

be known.

There are varieties of experimental techniques

that were used to determine the structure of DNA

Zaharim, W., Sulaiman, S., Abu Bakar, S., Ismail, N., Rozak, H. and Watanabe, I.

Density Functional Theory Studies on Guanine and Cytosine.

DOI: 10.5220/0008887000850091

In Proceedings of the 7th International Conference on Multidisciplinary Research (ICMR 2018) - , pages 85-91

ISBN: 978-989-758-437-4

nitrogenous bases such as NMR spectroscopy, X-ray

crystallography, and electron microscopy. The

experimental results are often compared with

theoretical results. Several research groups have

carried out theoretical study by using isolated bases

(hydrogen replace sugar phosphate) (Kilina et al.

2007) or methyl group (Mahanto et al. 2008) to

replace the sugar phosphate backbone. The use of

methyl group to replace sugar phosphate group that

is attached to the bases can be a justifiable

approximation as it can mimic the effect of sugar

phosphate group through hyperconjugation effects

(Mahato et al. 2008). However, methyl group is an

electron donating group that could increase electron

donating properties of the molecule (Pullman and

Pullman, 1958). Mahanto et al. also concluded that

that sugar phosphate group needs to be taken into

consideration when designing a calculation model

(Mahanto et al. 2008). The question on the effect of

methyl group and sugar phosphate group to the

electronic structure of the nitrogenous base is

therefore the motivation of this study.

In this paper, we report the results of our

computational investigation using DFT cluster

method to study the electronic structures of one of

the complementary base pairs which are guanine and

cytosine. The goal of this study is to investigate the

electronic structure of guanine and cytosine in two

different forms.

2 METHODOLOGY

The structural data for all four structures studied in

this investigation guanine nucleobase, guanine

nucleotide, cytosine nucleobase and cytosine

nucleotide were obtained from PubChem database

(Kim et al. 2015). Figure 1 represents guanine and

cytosine structures. The atoms numbering follows

Sinden et al. numbering scheme (Sinden et al. 1998).

The difference between nucleobase and

nucleotide structures is that for the former a methyl

group is attached at the R position, whereas for the

later a sugar phosphate group is attached as shown in

Figure 1. The structures of the methyl group and

sugar phosphate groups are shown in Figure 2. A

methyl group belongs to an organic family called an

alkyl group that contains one carbon atom

surrounded by three hydrogen atoms. Sugar

phosphate group is an important structural

component that forms the backbone of nucleic acids

such as DNA and RNA. A sugar phosphate group

consists of deoxyribose sugar that attaches to a

phosphate group.

Figure 1: DNA bases structures and numbering. (a)

guanine and (b) cytosine.

Figure 2: Methyl group and sugar phosphate structures. (a)

methyl group and (b) sugar phosphate.

DFT cluster method was applied to study the

electronic structures of all four structures. DFT

method is an alternative ab initio method that is

more efficient in considering correlation energy.

Hybrid functional is the most popular functional

used in DFT computations. One common functional

is B3LYP. Hybrid functional is effective functional

for organic, biochemical and large systems without

requiring an excessive amount of computing time,

memory and disk space (Rengifo and Murillo,

2012).

ICMR 2018 - International Conference on Multidisciplinary Research

The Cluster Method was employed

(Sulaiman et al. 2015) and the DFT quantum

mechanical procedure at B3LYP/6-311++G (d,p)

level (Izzati et al. 2011) was applied to investigate

the electronic structures. The chosen basis set

contains a polarization function which is important

to allow the distortion of the atomic orbitals in a

molecular environment. The 6-311++G basis set

used in our investigation has p-type function added

to hydrogen atom and d-type function added to all

other atoms. The diffuse function which is also

included in the 6-311++G (d,p) basis sets is to

allows the electron to move further away from the

nucleus in the ground state (diffuse functions were

added to all atoms). The extended basis set is needed

to produce a reliable result of the electronic structure

and total energy (Rengifo and Murillo, 2012). The

converged molecular orbitals were then used to

examine the electronic structures of the systems.

Gaussian 16 (G16) computational software

package installed at the RIKEN Hokusai Great

Wave Supercomputing facility was used to perform

the calculations. Gaussian 16 is the latest in the

Gaussian series of programs and has the capabilities

for electronic structure modelling (Frisch et al.

2016). There are a few types of calculation that can

be done by using this computational software such

as single point energy, geometry optimization,

Hartee-Fock and others.

Two types of calculations were performed in this

study, single point energy calculation and geometry

optimization calculation. Single point energy

calculations were made to compute the electronic

structure of the system and provide information

about the molecule such as energy, wave function

and charge distribution. The calculation is performed

at a single fixed geometry. On the other hand,

geometry optimization calculations were conducted

to determine the geometry of the molecules that is

the most stable with respect to the total energy. All

four structures were optimized such that the

optimized geometries correspond to the systems

with minimum total energy.

3 RESULT AND DISCUSSION

Following the main motivation of our computational

investigation, a systematic study on the electronic

structures of guanine and cytosine that are attached

to a methyl group or a sugar phosphate group has

been performed using the methodology presented

above.

3.1 Geometrical Parameters

All optimized structures preserved the planar

geometrical shape of the nitrogenous bases after

atomic relaxation. Figure 3 shows the changes in the

selected bond lengths of the optimized structure

relative to the initial structure, while Figure 4 shows

the changes in the selected bond angles. As can be

seen from Figure 3 and Figure 4, the trend of the

increases or decreases of the parameters are the

same for most atoms in nucleobases and nucleotides

form. The addition of methyl group or sugar

phosphate group results in similar effects to the bond

lengths and bond angles. The changes in the bond

lengths and bond angles do not result in any

significant modification to the planar shape of the

nitrogenous bases.

Figure 3: Bond length changes. (a) guanine and (b)

cytosine.

Density Functional Theory Studies on Guanine and Cytosine

Figure 4: Bond angles change of optimized structure. (a)

guanine and (b) cytosine.

3.2 Total Energy

The total energy of each molecule after geometry

optimization procedure is given in Table 1. The total

energy presented is relative to total energy obtained

from single point energy calculation. This result

indicates that the optimized structure is more stable

because it has a lower energy. Nitrogenous base with

attached sugar phosphate group experiences large

differences in the energy after geometry

optimization process. It is therefore very important

to perform geometry optimization procedure before

attempting to obtain the electronic structure of the

system studied.

Table 1: Total energy of guanine and cytosine.

Nitrogenous

base

Total energy (eV)

Nucleobase Nucleotide

Guanine - 0.584 - 1.029

Cytosine - 0.137 - 0.634

3.3 Charge Distribution

Mulliken population analysis and natural population

analysis are two population analyses that can be

used to determine charge distribution in a molecule.

Mulliken population analysis is the most common

population analysis that has been used due to its

simplicity (Šponer et al. 2001). In this study, we did

not use Mulliken population analysis to determine

the effective charge on the atoms because of the

result is dependent of the method and basis set

(Matczak, 2016). The charge distribution presented

in this study is based on the natural population

analysis.

Figure 5: Atomic charge distribution. (a) guanine and (b)

cytosine.

ICMR 2018 - International Conference on Multidisciplinary Research

The determination of charge distribution is

crucial in the study of the electronic structure of the

system. Atomic charge distribution can be used to

study the charge transfer in a chemical reaction.

Figure 5 represents the charge distribution value of

guanine and cytosine optimized structures. The

existence of methyl group and sugar phosphate

group does not give significant effect to the charge

distribution around the nitrogenous bases ring.

3.4 Ionization Energy

The calculated ionization energies for the optimized

structures are summarized in Table 2. From the

result, it can be seen that the ionization energy

increases by 0.364 eV when the methyl group is

replaced by a sugar phosphate group. Thus, it

requires more energy to remove an electron from the

latter molecule. In the case of cytosine, the

difference in the ionization energy between

nucleobase and nucleotide is not only relatively

small, but decreases, which is opposite in effect as

compared to the case of guanine.

From our calculation, guanine in nucleobase and

nucleotides configurations has lower ionization

energies as compared to cytosine. Our results are in

agreement with the statement of Senthilkumar et al.

(Senthilkumar et al. 2003). Considering that guanine

has a lower ionization energy, guanine base becomes

the main target for oxidation to occur (Seidel et al.

1996). From biological perspective, oxidation of

nitrogenous base promotes oxidative damage.

Table 2: Ionization energy of guanine and cytosine.

Nitrogenous

base

Ionization energy (eV)

Nucleobase Nucleotide

Guanine 5.849 6.258

Cytosine 6.462 6.459

3.5 Frontier Molecular Orbital

Analysis

The transfer of charge through the molecule is

affected by the electronic structure (Padmaja et al.

2009). In particular, the difference in the energy of

highest occupied molecular orbital (HOMO) and

lowest occupied molecular orbital (LUMO) is an

important parameter that is considered to study and

understand the possibilities of charge migration

through DNA. The surface plot of the calculated

HOMO and LUMO, and the corresponding energy

level diagram are shown in Figure 6 and to Figure 7.

The molecular orbital is presented on the surface

of equal amplitude of 0.020. From this plot, the

positive and negative sign wave function is indicated

by the red and green colour respectively. The sign of

the wave function on the nitrogenous base ring in

nucleobase and nucleotide configuration is opposite

from each other. It is clear that methyl group and

sugar phosphate groups have an impact on the

attributes of the molecular orbitals.

Figure 6: Molecular orbital surface plot and energy level

diagram of guanine. (a) guanine nucleobase and (b)

guanine nucleotide.

Density Functional Theory Studies on Guanine and Cytosine

Figure 7: Molecular orbital surface plot and energy level

diagram of cytosine. (a) cytosine nucleobase and (b)

cytosine nucleotide.

From the molecular orbital energy diagram, it

can be seen that all nucleobases and nucleotides

have a HOMO-LUMO gap of more than 5 eV. The

value of HOMO-LUMO gap for guanine

nucleobase, guanine nucleotide, cytosine nucleobase

and cytosine nucleotide are 5% lower, 9% lower, 1%

lower and 2% higher than Kilina et al. findings

respectively (Kilina et al. 2007). The sequence and

magnitude of the HOMO-LUMO gap for all

structure are guanine nucleobase < cytosine

nucleobase < guanine nucleotide < cytosine

nucleotide. Nucleobases structures have a lower

HOMO-LUMO gap. This is more likely due to the

presence of methyl group. Methyl group is an

electron donating group and could decrease the

HOMO-LUMO gap (Pullman and Pullman, 1958).

Structure with sugar phosphate group attached to the

nitrogenous base has a larger HOMO-LUMO gap.

Hence, it is clear that inclusion of sugar phosphate

group has an impact to the HOMO-LUMO gap. The

changes in the HOMO-LUMO gap could affect the

possibilities of charge transport through DNA.

3.6 Dipole Moment

The measurement of dipole moment is important in

differentiating polar and non-polar molecules.

Dipole moment is basically the measure of net

polarity in a molecule. Polar molecule has an uneven

charge distribution across the entire molecule.

Moreover, the polarity is determined by the

distribution of donor and acceptor functional group

around the base.

Guanine and cytosine are known as polar

molecules (Kilina et al. 2007). Table 3 summarizes

the values of dipole moment of guanine and cytosine

calculated using the optimized structures. From the

calculated dipole moment, the most polar base is

guanine. Cytosine has a lower dipole moment. For

guanine, the dipole moment of the nucleotide is

slightly larger than that for the nucleobase.

However, the trend is opposite for the case of

cytosine.

Table 3: Dipole moment of guanine and cytosine.

Nitrogenous

base

Dipole moment (D)

Nucleobase Nucleotide

Guanine 7.400 7.413

Cytosine 6.369 5.322

4 CONCLUSION

From our computational study, the presence of

methyl group or sugar phosphate group to the

nucleic acid bases has a direct effect on the structure

of the system. Further computational investigation

should be performed on adenine and thymine. A

comparison between all four bases is needed so that

we can have a better understanding on DNA

electronic structure and properties.

The computational method that was used in this

study can be employed for more complex oligomer

system. This study would be extended using bigger

cluster size with more bases so that the effects of

neighbouring bases can be included and studied.

ICMR 2018 - International Conference on Multidisciplinary Research

ACKNOWLEDGEMENTS

This research was supported by Universiti Sains

Malaysia through Research University grant (Grant

No: 1001/PJJAUH/870037. We would like to

acknowledge Hokusai Greatwave Supercomputing

facility (Project No. G18022) at RIKEN Advanced

Center for Computing and Communication. One of

us (W.N. Zaharim) would like to thank the Ministry

of Education, Malaysia for the award of MyBrain 15

fellowship.

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Density Functional Theory Studies on Guanine and Cytosine