Engineering, 2013, 5, 203-206 Published Online October 2013 (
Copyright © 2013 SciRes. ENG
In Silico Molecular Interaction Studies of Suberoylanilide
Hydroxamic Acid and Its Modified Compounds with
Histones Deacetylase Class II Homo sapiens as C urative
Measure towards C ervical Canc er
Usman Sumo Friend Tambunan1*, Arli Aditya Parikesit1, Tirtana Prasetia1, Djati Kerami2
1Department of Chemistry, Faculty of Mathematics and Science, University of Indonesia, Depok, Indonesia
2Department of Mathematics, Faculty of Mathematics and Science, University of Indonesia, Depok, Indonesia
Email: *
Received May 2013
The threat of cervical cancer is a serious problem for the women’s health. It is already known that the cause of cervical
cancer is definitely HP V (Human Papilloma Virus). The drug development is the most reasonable approach for coping
with HPV infection. The development of HDACi (Histon e Deacetylase inhib itor) is seen as a feasible method for curing
the threat of cervical cancer. Rational drug design is our utilized pipeline for drug development. The LigX MOE-based
method has been developed to investigate the molecular interaction of HDAC class II Homo sapiens with the designed
lead compound. The method has found that ligands 1c, 2a, and 2c are indeed feasible to be formulated as drug candi-
Keywords: Cervical Cancer; HPV; HDAC; S AHA; LigX; Dynamics Simulations
1. Introduction
The second most tangible cancer threat for woman is
cervical cancer that is caused by Human Papillomavirus
(HPV) [1,2]. There are several studies to date that strug-
gling to cope with HPV infection. The possible ap-
proaches are developing drugs and vaccine. To date,
there are numerous successful projects in HPV vaccine
and immunotheraphy development, and some of them
already reach the market [3-6]. Moreover, computational
approach of designing HPV vaccine is on sight as well
[7]. However, the vaccine could only feature as the pre-
vention agent, not curative one. In this end, drug devel-
opment is seen as one of the most promising methods of
curing HPV infection.
There are some anti-HPV drug development methods
in the market, but one of the feasible strategies for cer-
vical cancer therapy is the development of Histone dea-
cetylase inhibitor (HDACi) as the drug candidate [8,9].
The side effects of SAHA are well known in the medical
community by inhibiting immature osteoblasts [10]. Hence-
forth, the derivatives of SAHA have been developed for
mitigating those side effects. Moreover, the possible
modification on the SAHA functiona l groups is basically
The objective of this research is to investigate the mo-
lecular interaction of our designed ligands, as SAHA
modified compounds, with the HDAC class II Homo
sapiens. In this end, it is expected that this study will
pave a way for developing drug candidates.
2. Methods
The whole method was utilized based upon the procedure
in [11,12]. The 3D structure of Homo sapiens class II
HDAC was prepared. The integrity of the protein and
ligand structure was optimized with Linux script and
Autodock tools [13]. The molecular docking and dynam-
ics procedure were conducted in accordance to the estab-
lished method [11,12]. The stages of molecular dynamics
are initialization, equilibration, and production. In order
to study the molecular interaction, th e LigX tool of MOE
2008.10 wa s utiliz e d.
3. Results and Discussion
The designated pipeline has eventually produced the de-
sired result. The autodock visualization of the active site
of HDAC class II Homo sapiens was shown in Figu re 1.
It is shown that the active site was hidden in the inner
crevice. In this end, a sophisticated pipeline was needed
to observe the ligand interaction within the crevice itself.
Corresponding author.
Copyright © 2013 SciRes. ENG
Figure 1. Visualization of the active site of HDAC class II
Homo sapiens.
We have prepared the best ligand based upon the pre-
vious study that has the best affinity and the lowest tox-
icity in accordance to the Lipinski’s Rule of Fiv e [12,14].
Each HDAC will be paired with SAHA as its standard
and one best ligand in order to observe their molecular
interaction. The interaction pair between ligand and
HDAC could be observed in Table 1.
The existing drug development pipeline has designed
three SAHA-derived ligands, namely 1c, 2a, and 2c [11],
[12]. LigX, as an integrated tool of MOE packages, has
been utilized by scientific community to evaluate the
structure-based ligand optimization. The Figure 1 shows
that the Zn2+ ion interaction with existing residues is
stronger in our ligand than SAHA. Thus, it is a direct
evidence that metal-based cofactor plays a role in the
protein-ligand interaction [15]. The electron distribution
of our ligands is more favorable than the standard, as
shown in all instances of Figure 2, because the electron
cloud is distributed more equally in all atoms of our li-
gands. Observation of contact residues and hydrogen
bonding of those ligands have shown that they are indeed
suitable to be developed as HDACi, as the molecular
interaction is stronger than SAHA.
4. Conclusion
The computational effort of this study has shown that the
electronic interaction of the ligand with the receptor is
the main factor for the well being of a chemical reaction.
The molecular interaction study has shown that our li-
gands are indeed feasible to be developed as drug candi-
SAHA (standard) Our Ligands [11,12]
(a) (b)
(c) (d)
Copyright © 2013 SciRes. ENG
(g) (h)
(i) (j)
Figure 2. The molecular interaction visualization of LigX tools after molecular dynamics production session at 5000 ps for: (a)
HDAC4-SAHA; (b) HDAC4-2c; (c) HDAC5-SAHA; (d) HDAC5-2a; (e) HDAC6-SAHA; (f) HDAC6-2c; (g) HDAC7-SAHA;
(h) HDAC7-2c; (i) HDAC9-SAHA; (j) HDAC9-1c.
Table 1. The HDAC class II Homo sapiens pairing with the
Enzim Ligan
dates due to their strong affinities with the receptors.
5. Acknowledgements
The funding for the research and the conference is sup-
ported by Skema Bantuan Seminar Luar Negeri/Program
Insentif Peneliti Universitas Indonesia Tahun 2013
(BOPTN) Submission #1511 and Hibah BOPTN Ditjen
Dikti No: 2788/H2.R12/HKP.05.00/2013. Usman Sumo
Friend Tambunan and Djati Kerami supervised this re-
search; Tirtana Prasetia was working on the technical
details, while Arli Aditya Parikesit prepared the English
manuscript and re-verified the computation data.
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Copyright © 2013 SciRes. ENG
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