academic trip 2014 - universitas indonesia · 2014. 2. 17. · academic trip 2014 bioinformatics...
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ACADEMIC TRIP 2014 Bioinformatics Research Group, Universitas
Indonesia
National University of Singapore, University of Malaya
February
10th – 16th,
2014
Prof. Dr. Usman Sumo Friend Tambunan
Bioinformatics Research Group
February 10th – 16th, 2014
Patron : Dr. Ridla Bakrie, M.Phil
Steering Committee (SC) : Prof.Dr.Usman Sumo Friend Tambunan
Chairman of The Program/
Chairman of Organizing Committee : Dr.rer.nat Arli Aditya Parikesit
Treasurer/ad interim Secretary/
Vice Chairman OC : Hilyatuz Zahroh.,MSc
Public Relation and Event : Dwi Mustika Handayani, Dina Rahma Fadilah., B,Ed
Milda Paramitha., B.Ed, Niken Widayanti., B.Sc
Proceeding Team : Linggih Saputro, Titin Ariyani, and Rizkyana Avissa
Secretariate : Cipta Priyo Satryanto and Amalia Hapsari
Accomodation and Logistics : Arfin Fardiansyah
Opening Remarks from the Chairman of Department of Chemistry,
Faculty of Mathematics and Science, Universitas Indonesia
It is an honor for me to give my word about this academic trip. As the Chairman of Department of
Chemistry, Faculty of Mathematics and Science, Universitas Indonesia, I would like to express
my gratitude to bioinformatics research group of our Department of Chemistry in holding an
academic trip to National University of Singapore and University of Malaya.
Department of Chemistry is one of the top rank department in Universitas Indonesia. We proudly
achieved the high score in AUN Quality Assurance 2012 among departments in our university. In
order to improve the quality of our department, it is a good manner to build good relationship
between other university and research instituition world wide in order to expand and enrich our
knowledge.
Bioinformatics Research Group is the member of Department of Chemistry, Universitas Indonesia
whose researches are dealing with application of computational techniques in vaccine and drug
design. This group has already published publications in several international prestigious journals.
Not only its excellence in research, bioinformatics groups also organize some beneficial activities,
for instance an annual seminar by inviting International speakers and academic trip visiting
academic institution in other countries. Through this academic trip, I hope the member of
bioinformatics group would share their latest and best research as well as the students would get
experiences which can be shared to others.
Hereby, I want to congratulate Prof. Dr. Usman Sumo Friend Tambunan as the head of
Bioinformatics research group and his colleagues who has succeeded this academic trip. I would
like also to express my deepest gratitude to all departments and universities who have welcomed
our students and members to visit. Through this visit, I wish all of us could get the advantages, as
well as enhance and strengthen the relationship and cooperative framework between researchers
of chemistry and life sciences in South East Asia.
.
Opening Remarks from the Vice Dean of Faculty of Mathematics and Science
Universitas Indonesia
It is a high privilege for me to give a brief remark of this academic trip. First of all, as the vice
dean of the Faculty of Mathematics and Science, Universitas Indonesia, I would like to express
my gratitude to all member of academic institution which have been welcome our members and
students to expand their knowledge and experience.
Universitas Indonesia is aimed to be a world-class university. Hence, in order to actualize that aim,
we are challenged to increase our quality in research and publication, student activities, and other
matter up to international level. Furthermore, as a scientist, we need to make a good and strong
relationship with other research institution worldwide to communicate our research, so the future
research would be performed better.
This academic trip, which is organized by Bioinformatics research group, is a good idea which is
accord to those goals. By visiting academic institution in other countries and share the knowledge,
I hope the students and all members of the research group will obtain a good experience that could
give a motivation for all of us.
Furthermore, from the bottom of my heart, I would like to express my gratitude to all
bioinformatics research group member and especially to Prof. Dr. Usman Sumo Friend Tambunan,
as the head of the group, who made this event exist. Through this visit, I wish we could enhance
and strengthen the relationship and cooperative framework between researchers in life sciences in
South East Asia.
Bioinformatics Research Group’s Achievements in 2014 :
Updated : January, 30th, 2014
Published Journals
Tambunan, U.S.F.,Zahroh, H.,Bimmo B.U., Parikesit, A.A. 2014. Screening of Commercial Cyclic
Peptide as Inhibitor NS5 Methyltransferase of Dengue Virus through Molecular Docking and Molecular
Dynamics Simulation .Bioinformation, 10(1).
In press article:
Tambunan, U.S.F., Parikesit, A.A., Dephinto, Y., Sipahutar, F.R.P. 2014. Computational design of drug
candidates for influenza A virus subtype H1N1 by inhibiting the viral neuraminidase-1 enzyme. Acta
Pharmaceutica, 2/14 [In press]
Academic Venue
1. DUKE-National University of Singapore, Graduate School of Medicine
ABOUT NUS
National University of Singapore (NUS) is a leading global university centered in Asia
offering a global approach to education and research with a focus on Asian perspectives
and expertise.
Its 14 faculties and schools across three campus locations in Singapore – Kent Ridge, Bukit
Timah and Outram – provides a broad-based curriculum underscored by multi-disciplinary
courses and cross-faculty enrichment. NUS' transformative education includes programs
such as student exchange, entrepreneurial internships at NUS Overseas Colleges, and
double degree and joint degree programs with some of the world’s top universities. The
learning experience is complemented by a vibrant residential life with avenues for artistic,
cultural and sporting pursuits.
NUS shares a close affiliation with 22 university-level, 16 national-level and more than 80
faculty-based research institutes and centers. NUS is well-known for its research strengths
in engineering, life sciences and biomedicine, social sciences and natural sciences.
Integrating its core competencies of education and research with an entrepreneurial
dimension, NUS strives to create a supportive and innovative environment to promote
creative enterprise within its community.
NUS is actively involved in international academic and research networks such as the
Association of Pacific Rim Universities (APRU) and International Alliance of Research
Universities (IARU). This global networking further enhances its international presence
ABOUT DUKE UNIVERSITY
Duke University is one of the world's top institutions of higher education located in south-
eastern United States. Younger than most other prestigious U.S. research universities, Duke
University consistently ranks among the very best The university is well-known for cross-
disciplinary education and research.
The School of Medicine is also one of the largest biomedical research enterprises in the
United States. U.S. News & World Report, for example, has ranked Duke year after year
as being among the leaders in American medical education. It is ranked among the top 10
American medical schools in National Institutes of Health grant funding. With highly
respected research programs in areas ranging from cancer, heart disease and the basic
sciences to clinical trials and health policy research, Duke is home to the nation's largest
and oldest academic clinical research organization - the Duke Clinical Research Institute -
and to the Institute for Genome Sciences and Policy.
The School of Medicine is located on the Duke University Medical Center campus, located
adjacent to the main campus of Duke University in Durham, North Carolina. In addition to
the medical school, the campus includes Duke University Hospital, ranked near the top of
the Honor Roll of America's Best Hospitals by U.S. News & World Report, and the Private
Diagnostic Clinic.
Research is an intrinsic part of being one of the best medical schools in the world; it is
worked into the DNA of any good medical institution. At Duke-NUS, faculty staff and
students are given access to some of the world’s most sophisticated biomedical research
facilities. Duke-NUS focuses on 5 “Signature Research Programs”: Cancer and Stem Cell Biology,
Cardiovascular & Metabolic Disorders, Emerging Infectious Diseases, Health Services & Systems
Research, and Neuroscience and Behavioral Disorders.
Duke-NUS Graduate Medical School Singapore
8 College Road
Singapore 169857
Phone: +65 6516 7666 / Email: [email protected]
2. Department of Chemistry, Faculty of Science, University of Malaya
The University of Malaya ( UM) is a public research university located in Kuala
Lumpur, Malaysia. It is the oldest and top university in Malaysia. The university was
founded in 1949 as a public-funded tertiary institution. The University of Malaya has been,
and remains, at the forefront of landmark scientific and medical discoveries as is evidenced
by the numerous awards that have been won both locally and internationally.
UM researchers are in collaborative partnerships with more than 100 international
institutions working on diverse topics from HIV-AIDS, infectious diseases, biodiversity,
nanotechnology to law, intellectual property, culture, religion, gender studies and poverty
eradication studies. In the coming years, the university will see a further quantum leap in
high quality research activity and publications as a result of the huge research funding that
the university now enjoys from numerous sources and the many excellent students and staff
that they are now admitting.
UM researchers received the highest number of successful applications in the "Research
Co-operation" category of the United Kingdom Prime Minister's Initiative for International
Education (PMI-2) Connect Scheme with seven successful grants totalling GBP 230,385.
The awards were given in the fields of photonics, plasma laser physics, halocarbons and
climate change, group theory and mathematical cryptography, air-conditioning and
refrigeration engineering, molecular microbiology and biotechnology.
The Department of Chemistry is the largest department in the Faculty of Science. One of
the objectives of the department is to provide a centre of excellence in chemical education
and research in Malaysia.
Teaching and studying at the undergraduate and postgraduate levels, as well as research,
are supported by instrumentation. Some of the research units have their own specialized
equipments and computing facilities are excellent. The department equipped with advanced
instrumentation such as ICP-MS, LC-MS QTOF, GC-FID, FT-NMR, HPLC, PREP-LC,
GPC, TGA, GC, XRD, IC, Rheometer, FT-IR, UV Spectrometer, Photometric Dispersion
Analyser, Zetasizer Particale Sizer System, Drop Volume Tensionmeter, Liquid Capillary
System.
Chemistry Department, Faculty of Science,
University of Malaya,
50603 Kuala Lumpur
MALAYSIA
Phone number: +603-79674204
Fax number: +603-7967 4193
Email:
Program Outline
DATE ACTIVITY
Monday, February, 10th,
2014
Arrival at Changi Airport
Activity at Sentosa Island
Watching Song of The Sea Show
Tuesday, February, 11th,
2014
Visiting Orchard Road, Merlion Park, National
Museum of Singapore, Esplanade Theatre,
Gardens By The Bay, and Marina Bay Sands
Wednesday, February,
12th, 2014
Oral Presentation and Laboratory Visit at National
University of Singapore
Visiting Haw Par Villa
Visiting Clarke Quay
Thursday, February, 13th,
2014
Trip to Kuala Lumpur
Visiting Petronas Twin Tower, Lake Symphony
Visiting Malay for National Palace
Friday, February 14th,
2014 Oral Presentation and Laboratory Visit in
Universiti of Malaya
Saturday, February, 15th,
2014
Visiting Batu Caves
Visiting Sri Mahariamman Temple
Visiting Paragon
Sunday, February, 16th,
2014 Flight back to Indonesia
Prof. Dr. Usman Sumo Friend Tambunan D.Sc, Faculty of Science, Tohoku University, Sendai, Japan (1986)
M.Sc, Faculty of Science, Tohoku University, Sendai, Japan (1983)
B.Sc in Chemistry, University of Indonesia (1978)
Research Interest : vaccine and drug design, protein engineering, peptide based
drug design
CONTACT
ABSTRACT
Background: The cervical cancer is the second most
prevalent cancer for the woman in the world. It is
caused by the oncogenic human papilloma virus (HPV).
The inhibition activity of histone deacetylase (HDAC)
is a potential strategy for cancer therapy.
Suberoylanilide hydroxamic acid (SAHA) is widely
known as a low toxicity HDAC inhibitor. This research
presents in silico SAHA modification by utilizing
triazole, in order to obtain a better inhibitor. We
conducted docking of the SAHA inhibitor and 12
modified versions to six class II HDAC enzymes, and
then proceeded with drug scanning of each one of them.
Results: The docking results show that the 12 modified
inhibitors have much better binding affinity and
inhibitionpotential than SAHA. Based on drug scan
analysis, six of the modified inhibitors have robust
pharmacological attributes, as revealed by drug
likeness, drug score, oral bioavailability, and toxicity
levels.
IN SILICO MODIFICATION OF
SUBEROYLANILIDE HYDROXAMIC ACID
(SAHA) AS POTENTIAL INHIBITOR FOR
CLASS II HISTONE DEACETYLASE (HDAC)
Prof. Dr. Usman Sumo Friend Tambunan
Selected Publication
U.S.F. Tambunan., R. Bakri., T. Prasetia., A.A.
Parikesit.,and D. Kerami,. 2013. Molecular dynamics
simulation of complex Histones Deacetylase (HDAC) Class
II Homo Sapiens with suberoylanilide hydroxamic acid
(SAHA) and its derivatives as inhibitors of cervical cancer,
Bioinformation. 9:696–700
U.S.F.Tambunan,. D.F. Witanto,. and A. A.
Parikesit.2012.In silico Genetics Variation Pathogenecity
Analysis of hemagglutinin, Matrix 1, an non structural 1
protein of Human H5N1 Indonesian .IIOAB. 3(3): 5-14
Conclusions: The binding affinity, free energy
and drug scan screening of the best inhibitors
have shown that 1c and 2c modified inhibitors
are the best ones to inhibit class II HDAC.
DR. Ridla Bakri, M.Phil Doctoral in Chemistry, University of Newcastle Upon Tyne, UK (1997)
Master Degree in Chemistry, University of Newcastle Upon Tyne, UK (1993)
Master Degree in Chemistry, University of Indonesia(1984)
Bachelor in Chemistry, University of Indonesia (1980)
Research Interest : Inorganic Chemistry
CONTACT
ABSTRACT
Cervical cancer is second most common cancer in
woman worldwide. Cervical cancer caused by human
papillomavirus (HPV) oncogene. Inhibition of histone
deacetylase (HDAC) activity has been known as a
potential strategy for cancer therapy. SAHA is an
HDAC inhibitor that has been used in cancer therapy
but still has side effects. SAHA modification was
proposed to minimize side effects. Triazole attachment
on the chain of SAHA has been known to enhance the
inhibition ability of SAHA and less toxic. In this study,
it will be carried out with molecular dynamic
simulations of SAHA modifications consisting of
ligand 1a, 2a and, 2c to interact with six HDAC in
hydrated conditions. To all six HDAC Class II,
performed docking with SAHA and a modified
inhibitor. The docking results were then carried out
molecular dynamics simulations to determine the
inhibitor affinities in hydrated conditions. The
molecular dynamic simulations results show better
affinities of ligand 2c with HDAC 4, 6, and 7 than
SAHA itself, and good affinity was also shown by
ligand 2a and 1c on HDAC 5 and 9. The results of this
study can be a reference to obtain better inhibitors.
MOLECULAR DYNAMICS SIMULATION OF
COMPLEX HISTONES DEACETYLASE
(HDAC) CLASS II Homo sapiens WITH
SUBEROYLANILIDE HYDROXAMIC ACID
(SAHA) AND ITS DERIVATIVES AS
INHIBITORS OF CERVICAL CANCER
*Collaboration with Tirtana Prasetia
Selected Publication
U.S.F. Tambunan., R. Bakri., T. Prasetia., A.A.
Parikesit.,and D. Kerami,.2013. Molecular dynamics
simulation of complex Histones Deacetylase (HDAC) Class
II Homo Sapiens with suberoylanilide hydroxamic acid
(SAHA) and its derivatives as inhibitors of cervical cancer,
Bioinformation. 9:696–700
R. Bakri, et all. 2012. Rational Addition of Capping
Groups to the Phosphomolybdate Keggin Anion
[PMo12O40]3− by Mild, non-Aqueous Reductive
Aggregation. Chem. Commun.48: 2779-2781
Keywords: Cervical cancer, HPV, HDAC,
Triazole, SAHA, Modified inhibitor, Docking,
Dynamic.
Dr. rer.nat Arli Aditya Parikesit Ph.D in Informatics, Institute of Computer Science, Leipzig, Germany (2012)
M.Sc in Chemistry, University of Indonesia (2006)
B.Sc in Chemistry, University of Indonesia (2004)
Research Interest : Biochemistry, Biotechnology, Bioinformatics
CONTACT
http://www.chem.ui.ac.id/research/biokimia/bioinformatika/eng
ABSTRACT
Cervical cancer ranks third as the most common deadly
cancer in women worldwide and ranks first in developing
countries. It is caused by human papillomavirus (HPV)
infection which has E6 and E7 oncoproteins that induce
epigenetic regulation including overexpression of histone
deacetylases (HDACs) gene leading to cervical
carcinogenesis. Thus HDACs becomes potential inhibition
target for cervical cancer treatment. In this study, a novel
series of 4-[(2-oxo-1,3-thiazolidin-3-yl)carbonyl]aniline
derivatives were designed as novel HDAC inhibitors
(HDACIs) based on de novo approach. The inhibitory
activity of these new designed ligands against Homo sapiens
class II HDAC was determined by molecular docking
simulation. All eight best ligands meet Lipinski’s rule of
five, have a better drug score than standards, and shows
good bioactivity, oral bioavailability and ADMET
properties. All best ligands also have a good synthetic accessibility and
were proved to be new compounds that never been
synthesized before. Stability of HDAC-ligand complexes in
the presence of solvent were also calculated through
molecular dynamics (MD) simulation. Based on this
simulation, all best ligands complex with corresponding
HDAC have a good stability based on RMSD (root mean
square deviation) and interaction analysis.
IN SILICO IDENTIFICATION OF 2-OXO-1,3-
THIAZOLIDINE DERIVATIVES AS NOVEL
INHIBITORS OF CANDIDATE OF CLASS II
HISTONE DEACETYLASE (HDAC) IN
CERVICAL CANCER TREATMENT
*Collaboration with Abi Sofyan Ghifari
Selected Publication
Tambunan U.S.F., N. Amri., and A. A.Parikesit.. 2012. In silico
design of cyclic peptides as influenza virus, a subtype H1N1
neuraminidase inhibitor. African Journal of Biotechnology.
11(52):11474-11491.
Tambunan U.S.F., R. Harganingtyas., and A.AParikesit.2012. In
silico Modification of (1R, 2R, 3R,5S)-(-)-
Isopinocampheylamine as Inhibitors of M2 Proton Channel in
Influenza A Virus Subtype H1N1, using the Molecular Docking
Approach. Trends in Bioinformatics. 5(2): 25-46
The best ligands can be synthesized for further
clinical testing. This study is expected to produce
more potent HDAC inhibitors as novel drugs for
cervical cancer treatment
Keywords: cervical cancer, de novo design,
HDAC, HPV infection, molecular docking,
molecular dynamics, QSAR analysis.
Hilyatuz Zahroh, B.Sc, MA, M.Sc Biochemistry, Bogor Institute of Agriculture (2002-2006)
Islamic Law, Institut Ilmu Al-Qur’an (2009-2011)
Biotechnology, University of Indonesia (2012-2014)
Research Interest : Biochemistry, Biotechnology, Bioinformatics
CONTACT
ABSTRACT
Dengue is an infectious disease caused by dengue virus
(DENV) and transmitted between human hosts by
mosquitoes. Nowadays, Indonesia is recorded as a
country with the highest cases of dengue in ASEAN.
Current treatment for dengue disease is supportive
therapy; there is no antiviral drug against dengue
available on the market. Therefore, the research about
antiviral drug against dengue is very important,
especially to prevent the outbreak explosion. In this
research, the development of dengue antiviral is
conducted through the inhibition of β-OG binding
pocket on Envelope protein of DENV by using analogs
of β-OG pocket binder. There are 828 compounds used
in this study and all of them were screened based on the
analysis of molecular docking, pharmacological
character prediction of the compounds and molecular
dynamics simulation. The result of these analyses
revealed the compound that can be used as an antiviral
candidate against dengue virus is 5-(3,4-
dichlorophenyl)-N-[2-(p-tolyl)benzotriazol-5-yl]furan-
2-carboxamide.
Keywords: Dengue, β-OG pocket, Envelope protein,
fusion inhibitor, molecular dynamics
SCREENING ANALOGS OF β-OG POCKET
BINDER AS FUSION INHIBITOR OF DENGUE
VIRUS 2
Hilyatuz Zahroh
Selected Publication
Tambunan U.S.F., H. Zahroh., B.B. Utomo., and A.A Parikesit.
2014. Screening of Commercial Cyclic Peptide as Inhibitor NS5
Methyltransferase of Dengue Virus through Molecular Docking
and Molecular Dynamics Simulation. Bioinformation. 10(1)
Parikesit A.A.,H.Zahroh., A.Hapsari.,and U.S.F. Tambunan.
2013. The Computation of Cyclic Peptide with Prolin-Prolin
Bond as Fusion Inhibitor of DENV Envelope Protein through
Molecular Docking and Molecular Dynamics Simulation.
International Conference on Biological Sciences Proceeding
(Accepted).
H.Zahroh., A.A Parikesit, C.P. Satriyanto, and U.S.F.
Tambunan. 2013. The In silico binding interaction of
Oseltamivir Derivatives with H7N9 Haemagglutinin and
Neuraminidase. ITB Journal (International Seminar on Tropical
Bioresources Proceeding). (Accepted)
Cipta Priyo Satriyanto, B.Sc B.Sc in Chemistry, University Of Indonesia (2014)
Research Interest : HDAC inhibitor for cervical cancer treatment,
organoboron
CONTACT
ABSTRACT
Histone deacetylase (HDAC) plays critical functions in
the regulation of gene expression. Recent studies
revealed that HDAC also has important role in
carcinogenesis. The inhibition of HDAC has emerged
as a new interesting area of anticancer research that
targets the biological processes including cell cycle,
apoptosis and differentiation. In this research, a
commercially available inhibitor of HDAC known as
SuberoylAnilide Hydroxamic Acid (SAHA) were
modified in order to improve its efficacy and reduce its
side effects. The hydrophobic cap and zinc-binding
group of this compound were substituted by boron-
based compounds, while its linker region was modified
by p-aminobenzoic acid. Molecular docking simulation
was conducted on SAHA and its derivatives to obtain
potential ligands with the lowest ∆Gbinding. Docking
analysis revealed 8 potential ligands with far more
negative ∆Gbinding than standards, SAHA and TSA, they
are Nova2(9058064-6), Nova2(95752-88-8),
Nova2(88765-82-6), Nova2(unique10), Nova2(16876-
27-0), Nova2(513246-99-6), Nova2(unique80), and
Nova2(279262-23-6).
All of these ligands were analyzed according to
their QSAR (quantitative structure-activity
relationship), pharmacological analysis and
ADME-Tox (absorption, distribution,
metabolism, excretion and toxicity) to obtain
potential inhibitor of HDAC class II Homo
sapiens. This multistep screening process
generated one best ligand, Nova2(513246-99-6),
which was further studied by means of
molecular dynamics simulation.
Keywords: QSAR analysis, Boron, HPV,
cervical cancer, molecular docking, molecular
dynamics
Selected Publication
H. Zahroh., A.A Parikesit., C.P Satriyanto., and U.S.F
Tambunan. 2013. The In silico binding interaction of
Oseltamivir Derivatives with H7N9 Haemagglutinin and
Neuraminidase. ITB Journal (International Seminar on Tropical
Bioresources Proceeding). (Accepted)
THE USE OF BORON COMPOUND TO MODIFY
SUBEROYL ANILIDE HYDROXAMIC ACID
(SAHA) AS HOMO SAPIENS HISTONE
DEACETYLASE (HDAC) CLASS II INHIBITOR
Cipta Priyo Satriyanto
Amalia Hapsari, B.Sc B.Sc in Chemistry, University Of Indonesia (2014)
Research Interest : biochemistry, drug research & development,
health and nutrition
CONTACT
ABSTRACT
Cervical cancer has high rate of mortality in Indonesia
every year. Because of that, it is important to find a
better drug of anti-cancer for cervical cancer this time,
and natural product from Indonesian biota be expected
become one of a kind. It has purpose to increase the
utilization of Indonesian natural resources. Cervical
cancer curing can be done by analyzing the mechanism
of Human papillomavirus (HPV), cervical cancer virus,
towards human body. Evidently, HPV can induce
deacetylation process by Histone Deacetylase (HDAC),
deacetylation can disrupt gene transcription, and so
inhibit this process by HDAC inhibitor becomes a
solution. Interaction between HDAC and HDAC
inhibitor can be analyzed by computation method,
afterward it was screened by the parameters, with the
result that Herbaric Acid becomes the best drug lead for
cervical cancer therapy.
Keyword: Cervical cancer, natural products, Histone
Deacetylase (HDAC), HDAC inhibitor, screening
SCREENING DATABASE OF INDONESIAN
NATURAL PRODUCTS AS POTENTIAL
INHIBITOR HISTONE DEACETYLASE
(HDAC) CLASS II HOMO SAPIENS FOR
CERVICAL CANCER THERAPY
Amalia Hapsari
Selected Publication
Parikesit A.A., H. Zahroh., A. Hapsari., and U.S.F
Tambunan.2013. The Computation of Cyclic Peptide with
Prolin-Prolin Bond as Fusion Inhibitor of DENV Envelope
Protein through Molecular Docking and Molecular Dynamics
Simulation. International Conference on Biological Sciences
Proceeding. (Accepted).
Dina Rahma Fadlilah, B.Ed Biotechnology, University Of Indonesia (2012 – present)
B.Ed in Biology, State University of Jakarta, Indonesia (2007-2012)
Research Interest : HDAC inhibitor for cervical cancer treatment
CONTACT
ABSTRACT
Cervical cancer is an epigenetic disease or abnormality caused by Human papillomavirus (HPV).
Globally, it is the third most deadly cancer threat for woman and also the most common cancer found in
Indonesia. To date, chemotherapy is a palliative treatment aimed at prolonging survival and improving
quality of life. HDAC inhibitor is the most promising chemotherapy agent. One of them, Suberoylanilide
hydroxamide acid (SAHA) has been approved by Food and Drug Administration (FDA). Unfortunately,
the use of SAHA cause several dangerous side effects. In this research, SAHA was modified by utilizing
Titanocene-based compounds. So far, approximately 2000 compounds has been designed and all of them
will be screened according to molecular docking simulation, pharmacological character prediction of the
compounds and molecular dynamics simulation.
Keywords: Cervical cancer, Human papillomavirus (HPV), HDAC inhibitor, Titanocene,
Molecular dynamics.
IN SILICO STUDY OF TITANOCENE-BASED SUBEROYLANILIDE HYDROXAMIC
ACID (SAHA) ANALOGUES AS POTENT Homo sapiens CLASS II HISTONE
DEACETYLASE INHIBITORS ON CERVICAL CANCER
Dina Rahma Fadlilah
Milda Paramita, B.Ed Biotechnology, University Of Indonesia (2012 – present)
B.Ed in Chemistry, State University of Padang, Indonesia (2008-2012)
Research Interest : HDAC inhibitor for cervical cancer treatment
CONTACT
ABSTRACT
Cervical cancer is the third mostly diagnosed cancer in females worldwide and also the common
cancer caused of cancer death in Indonesia. Cervical cancer is a disease caused by Human papillomavirus.
Nowadays, chemotherapy is well known as promising treatment for cervical cancer patient in order to
reduce growth rate of cancer cell. Target of therapeutic agent is apoptosis pathways. Inhibition of HDAC
is the one of potential strategic for cancer therapy. US FDA has approved Suberoylanilide Hydroxamic
Acid (SAHA) as HDAC inhibitor for cervical cancer treatment, but the drug still has side effects.
Recently, modified SAHA-ferrocene based as known as Jay Amin Hydroxamic Acid (JAHA) has tested
in vitro experiment on Triple-Negative MDA-MB231 Breast Cancer Cells. In this research, JAHA and
its derivative will be tested in silico experiment using Histone Deacetilases class II Homo sapiens for
cervical cancer treatment. So far, approximately 5000 compounds has designed and all of them would be
screened by using molecular docking simulation, pharmacological character prediction of the compounds
and molecular dynamics simulation.
Keywords: Cervical cancer, Human papillomavirus (HPV), HDAC inhibitor, Ferrocene, Molecular
dynamics.
IN SILICO EXPERIMENT OF MODIFICATION JAY AMIN HYDROXAMIC ACID
(JAHA) AS HISTONE DEACETYLASES (HDAC) INHIBITOR CLASS II Homo sapiens
USING MOLECULAR DOCKING AND MOLECULAR DYNAMICS APPROACH
Milda Paramita
Niken Widiyanti, B.Sc Biotechnology, University Of Indonesia (2012 – present)
B.Sc in Chemistry, State University of Jakarta, Indonesia (2008-2012)
Research Interest : HDAC inhibitor for cervical cancer treatment
CONTACT
ABSTRACT
Cervical cancer is the second largest cause of cancer-related death in women worldwide, with incidence
of 25-40 per 100,000 women per year. Recent studies has suggested the role of Histone Deacetylase
(HDAC) in the progression of carcinogenesis. Therefore, inhibition of HDAC activity could serve as a
potential strategy for cancer therapy. Largazole is a despeptide cyclic compound which has a structure
similar to FK228 orromidepsin, a natural product compound contained in commercial chemotherapeutic
drug, Istodax. However, it has been reported that largazole is a better HDAC inhibitor than FK228. This
study will modify largazole on its hydrophobic cap and linker using its active form, largazole thiol. The
screening of modified compounds of largazole is conducted using molecular docking method. In addition,
in vitro assay is also performed using HDAC Inhibition Assay Kit (colorimetric) and performed after
completed in silico assay. In silico assay also performed in a number of best modified compound of
largazole for pharmacological properties and toxicity where the results are compared with some other
HDAC inhibitor compounds, namely largazole, romidepsin, largazolethiol, romidepsinthiol and SAHA
and TSA as a standard inhibitor. The three best are selected based on the results of ligand docking
predictions and the ease of synthesis is then performed using the Synthetic Accessibility Prediction. The
aim of this research is to produce a potent inhibitor of the enzyme Histone Deacetylase (HDAC) class I
Homo sapiens as a potential cervical cancer therapy
Keywords: Cervical cancer, Human papillomavirus (HPV), HDAC inhibitor, Largazole, Molecular
dynamics, cyclic peptide, inhibition assay
INHIBITION ASSAY OF MODIFIED COMPOUND OF LARGAZOLE AS A POTENT
INHIBITOR OF HDAC CLASS I Homo sapiens
Niken Widiyanti
Linggih Saputro Chemistry, University Of Indonesia (2010 – present)
Research Interest : bioinformatics, cancer stem cell,
signaling pathway
CONTACT
ABSTRACT
Cervical cancer is the second most common cancer in women worldwide. Human papillomavirus
infection initiate the cancer but one of malignancy factors is caused by oncoprotein E6 and E7 which
activate Wnt/β-catenin signaling pathway. By inhibiting tankyrase, inhibitors like XAV939, JW55, and
others will stabilize axin then degrade this pathway. Screening inhibitors from database in silico could be
potential to select which inhibitor is the best one for the cervical cancer therapy.
Keywords: Cervical cancer, Human papillomavirus (HPV), Wnt/β-catenin signaling pathway,
tankyrase, inhibitor, screening
IN SILICO SCREENING DATABASE OF TANKYRASE INHIBITORS FOR CERVICAL
CANCER TREATMENT
Linggih Saputro
Dwi Mustika Handayani Chemistry, University Of Indonesia (2010 – present)
Research Interest : drug design, neuraminidase inhibitor for
influenza treatment, bioactive natural product
CONTACT
SCREENING DATABASE OF FLAVONOID COMPOUNDS AND DERIVATIVES AS
NEURAMINIDASE INHIBITOR H5N1 THROUGH MOLECULAR DOCKING AND
DYNAMIC SIMULATION
Dwi Mustika Handayani
ABSTRACT
Avian influenza pose a significant threat for animal and human health worldwide. Genetic variety
of avian influenza makes the disease become pandemic. Avian Influenza virus subtype H5N1 belonging
to Highly Pathogenic Avian Influenza (HPAI) has caused massive mortality on poultry and human since
1997. Neuraminidase, viral enzyme possessing a significant role in releasing virus progeny from infected
cell, has been a promising target to discover and develop an antiviral agent for avian influenza treatment.
Oseltamivir is one of neuraminidase inhibitor that is recommended by Centers of Disease Control and
Prevention (CDC) and World Health Organization (WHO) as antiviral agent against avian influenza. But,
oseltamivir resistance of H5N1 has been detected due to several mutation. Meanwhile, several studies
have shown that several flavonoid compounds possess inhibitory activity against neuraminidase. This
research is aimed to find the more potent neuraminidase inhibitor by screening database of flavonoid
compounds through molecular docking and dynamic simulation. QSAR (quantitative structure-activity
relationship) analysis of these compounds including pharmacology properties, bioactivity, mutagenicity-
carcinogenicity, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties
will be performed in silico
Keywords: avian influenza, H5N1, molecular docking, molecular dynamics, neuraminidase
inhibitor, flavonoid
Titin Ariyani Chemistry, University Of Indonesia (2010 – present)
Research Interest :HDAC inhibitor for cervical cancer treatment,
organoselenium
CONTACT
ABSTRACT
Cervical cancer is the second most common cancer among women and the seventh most common cancer
in the world. It is caused by Human Papilloma Virus (HPV) infection which has E6 and E7 oncoproteins
that induce the overexpression of histone deacetylases (HDACs) gene leading to cervical carcinogenesis.
Thus HDACs becomes potential inhibition target for cervical cancer treatment. Vorinostat or
suberoylanilide hydroxamic acid (SAHA) is the first histone deacetylase inhibitor approved by the
U.S. Food and Drug Administration (FDA) to inhibit HDACs activity, but may cause side effects. This
research is aimed to find the more potent HDACs inhibitor by modifying SAHA with organoselenium
compounds. To be able to compare the potency of the drug that has been modified, it is also used other
drugs as standard, such as trichostatin A (TSA), and valproic acid (VPA). QSAR analysis (quantitative
structure-activity relationship), ADMET test (absorption, distribution, metabolism, excretion, toxicity),
ease of synthesis prediction will be performed.
Keywords: Cervical cancer, Human papillomavirus (HPV), HDAC inhibitor, screening,
organoselenium
IN SILICO MODIFICATION OF SUBEROYLANILIDE HYDROXAMIC ACID (SAHA) WITH
ORGANOSELENIUM AS POTENTIAL INHIBITORS OF CLASS II HISTONE
DEACYTELASE (HDAC) IN CERVICAL CANCER TREATMENT
Titin Ariyani
Rizkyana Avissa Chemistry, University Of Indonesia (2010 – present)
Research Interest : bioinformatics, bioactive natural products,
medicinal chemistry
CONTACT
ABSTRACT
Avian Influenza subtype H5N1 is one of the most pathogen strains of Influenza A virus. According to
WHO, during 2003-2013, 641 case of HPAIV (Highly Pathogenic Avian Influenza Virus) H5N1 virus infection in
human occurred all over the world and caused mortality in 59% of the patient. Furthermore, the risk of mortality
and pathogenicity of H5N1 virus is increased by the increasing number of confirmed mutation of the isolated H5N1
viruses lead to resistance of some anti-influenza drugs. The mutations also occur in Neuraminidase, which is
important in spreading and pathogenicity of the virus, causing the urgent need of new neuraminidase inhibitor.
Natural products have been reported to be promising drug-like compound combating influenza A. In this research,
natural products group of stilbenoid used as neuraminidase inhibitor of H5N1 virus using in silico method.
Stilbenoid structure of various kinds of plants collected and screened through molecular docking against
Neuraminidase H5N1. The structure tested for toxicity test and Lipinski rule, and molecular docking.
Keywords: avian influenza, H5N1, molecular docking, molecular dynamics, neuraminidase
inhibitor, stilbenoid
SCREENING OF NATURAL STILBENOID COMPOUNDS AS NEURAMINIDASE
INHIBITOR H5N1 USING IN SILICO METHOD
Rizkyana Avissa
Mochammad Arfin Fardiansyah Nasution Chemistry, University Of Indonesia (2010 – present)
Research Interest : bioinformatics, hedgehog signaling pathway,
synthetic organic chemistry
CONTACT
DE NOVO DESIGN OF 1-TOSYLPIPERAZINE DERIVATIVES AS POTENTIAL
HEDGEHOG SIGNALING PATHWAY INHIBITOR FOR CERVICAL CANCER
THERAPY
Mochammad Arfin Fardiansyah Nasution
ABSTRACT
Cervical cancer ranks second as the most common deadly cancer in women worldwide and ranks
first in developing countries. However there is no effective treatment yet for this disease. Therefore it is
necessary to find a better drug for the cervical cancer treatment. Cervical cancer caused by Human
papillomavirus (HPV) infection which has E6 and E7 proteins that activate the Hedgehog (Hh) signaling
pathway and regulate cervical cancer cells proliferation, survival and migration. In this study, a novel
series of 1-tosylpiperazin derivates were designed as the potential inhibitors candidates of the sonic
hedgehog (Shh) signaling pathway. All of the potential inhibitors are going to be analyzed and compared
with HDAC’s commercially available inhibitors, SAHA and TSA, through molecular docking and
dynamics. QSAR (quantitative structure-activity relationship), pharmacological analysis and ADMET
properties examination will be conducted as well.
Keywords: Cervical cancer, Human papillomavirus (HPV), Hedgehog signaling pathway, inhibitor,
de novo, 1-tosylpiperazine
Thank You
Bioinformatics Research Group