Saran

BAB V. KESIMPULAN DAN SARAN

B. Saran

Protokol yang dikembangkan oleh Radifar et al. (2013) memiliki ruang

untuk pengembangan sehingga dapat mengenali senyawa-senyawa alam yang

terbukti aktif pada REα dan perlu dilakukan simulasi penambatan senyawa

modifikasi genistein terhadap REα.

67

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Alpha-Positive and Estrogen Receptor Alpha-Negative Human Breast

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Structure-based Design of Eugenol Analogs as Potential Estrogen

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http://www.who.int/cancer/detection/breastcancer/en/index1.html. diakses

pada tanggal 8 januari 2014.

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Proteasome-mediated Receptor Degradation, Dissertation, 4, Indiana

University, India.

Bielska, E., Lucas, X., Czerwoniec, A., Kasprzak, J.M., Kaminska, K.H.,

Bujnicki, J.M., 2011, Virtual Screening Strategies in Drug

Design-Methods and Applications, Journal of Biotechnology, Computational

Biology and Bionanotechnology, pp. 252.

Braun, C. A., Anderson, C. M., 2007, Pathophysiology: functional alterations in

human health, Lippincott Williams & Wilkins, USA, pp. 156, 157.

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Virtual Screening for Drug Discovery: a Problem-Centric Review,

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Chemical Libraries for Drug Discovery, Current Opinion in Chemical

Biology, pp. 194.

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USA, pp. 470, 474.

Hayashi, S-I., Eguchi, H., Tanimoto, K., Yoshida, T., Omoto, Y., Inoue, A.,

Yosida, N., Yamaguchi, Y., 2003, The Expression and Function of

Estrogen Receptor α and β in Human Breast Cancer and Its Clinical

Herynk, M.H., Selever, J., Thirugnanasampanthan, J., Cui, Y., Fuqua, S.A.W.,

2009, Hormone Action and Clinical Significance of the Estrogen Receptor

Alpha, Springer, pp. 1.

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Function, Kluwer Academic Publishers, pp. 193, 194.

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Characterization of Estrogenicity of Phytoestrogen in an

Endometrial-derived Experimental Model, Environmental Health Perspectives, pp.

582-583.

Huang, N., Shoichet, B.K., Irwin, J.J., 2006, Benchmarking Sets for Molecular

Docking, Jounal Medicine Chemistry, pp. 1-3.

Hwang, S. Y., Chang, S. J., Park, B. W., 2013, Does Chemotherapy Really Affect

the Quality of Life of Women with Breast Cancer?, Journal of Breast

Cancer, pp. 2.

Korb, O., Stützle, T., Exner, T.E., 2006, PLANTS: Application of Ant Colony

Optimization to Structure-Based Drug Design, Springer, pp. 4,6.

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312.

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Epigenetic Reactivation of Estrogen Receptor-α (ERα) by Genistein

Enhances Hormonal Therapy Sensitivity in ERα-Negative Breast Cancer,

Biomed Central Ltd, pp. 1.

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using PyMOL, J. Comput. Aided Mol. Des., 25, 13-9.

Marcou, G., Rognan, D., 2006, Optimizing Fragment and Scaffold Docking by

Use of Molecular Interaction Fingerprints, Journal Chemistry, pp. 195.

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Soybean and Health, pp. 329.

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Strategies for Hit-Finding and Optimization of Hepatitis C Virus (HCV)

Inhibitors, Current Medical Chemistry, pp. 2612.

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Receptor (ER) β1 and ERβcx/β2 Inhibit ERα Function Differently in

Breast Cancer Cell Line MCF7, Nature Publishing Group, pp. 5011, 5012.

Park, C.E., Yun, H., Lee, E.B., Min, B.I., Bae, H., Choe, W., Kang, I., Kim, S.S.,

Ha, J., 2010, The Antioxidant Effects of Genistein are Associated with

AMP-Activated Protein Kinase Activation and PTEN Induction in

Prostate Cancer Cells, Journal of Medicinal Food, pp. 815-820.

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Review of In Vitro and In Vivo Data, Acta Poloniae Pharmaceutica, pp.

136.

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Soya, Journal Chemistry, pp. 4-23.

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Computing, R foundation for Statistical Computing, Vienna.

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Protein-Ligand Interaction Fingerprinting, Bioinformation, pp. 325-327.

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Cancer Cells by Sulforaphane, Dissertation, 4-8.

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Isoflavone Genistein, Cancer and Metasis Reviews, pp. 265-280.

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Greene, G.L., 1998, The Structural Basis of Estrogen

Receptor/Coactivator Recognition and the Antagonism of This Interaction

by Tamoxifen, Cell Press, pp. 927, 928.

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Compounds on Tumor Promoter-Induced Activation of the Human

CYP1A2 Enhancers, Archive of Biochemistry and Biophysics, pp.

287-294.

Yang, T. L., Wu, T. C., Huang, C. C., Huang, P. H., Chung, C. M., Lin, S. J.,

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70

Lampiran 1. Hasil Analisa Statistik dengan R 3.0.1

> mean (filter$score)

[1] 0.4255475

> sd (filter$score)

[1] 0.1129547

> median (filter$score)

[1] 0.458

> shapiro.test(filter$score)

Shapiro-Wilk normality test

data: filter$score

W = 0.7826, p-value < 2.2e-16

> var.test(filter$score,std)

F test to compare two variances

data: filter$score and std

F = Inf, num df = 2768, denom df = 2768, p-value < 2.2e-16

alternative hypothesis: true ratio of variances is not equal to 1

> wilcox.test(filter$score, 0.6, var.equal=F, alternative="less")

Wilcoxon rank sum test with continuity correction

data: filter$score and 0.6

W = 0, p-value = 0.04027

Lampiran 2. Script yang digunakan untuk menambatkan genistein pada REα

#!/bin/sh

alias plants='/home/enade/program/PLANTS/PLANTS1.2'

alias pyplif='/home/enade/.pyplif/pyplif.py'

mkdir -p Docking/ERa-genistein

cd Docking/

for i in $(seq 1 3);

do mkdir ERa-genistein/replication_$i

cd ERa-genistein/replication_$i

for j in $(seq 1 1000);

do mkdir dock_$j

cd dock_$j/

cp /home/kenny/Skripsi/Fileconfig/plants/plants.config .

cp /home/kenny/Skripsi/Fileconfig/plants/protein.mol2 .

cp /home/kenny/Skripsi/Fileconfig/plants/genistein.mol2 .

cp /home/kenny/Skripsi/Fileconfig/plants/water.mol2 .

cp /home/kenny/Skripsi/Fileconfig/pyplif/config.txt .

cp /home/kenny/Skripsi/Fileconfig/pyplif/OHT.mol2 .

cp /home/kenny/Skripsi/Fileconfig/pyplif/ER_site.mol2 .

plants --mode screen plants.config

pyplif

rm plants.config protein.mol2 genistein.mol2 water.mol2

config.txt ER_site.mol2 OHT.mol2

grep results pyplif.csv > nohead.csv

awk '{if(substr($4.103.1)=="1") {print $1.$2.$3} else

{print "N/A"}}' nohead.csv > filter_asp.csv

echo dock_$j >> ../docklist.txt

cd ../

done

cd ../../

done

Lampiran 3. Script yang digunakan untuk filtrasi nilai Tc-PLIF filter terbaik

#!/bin/bash

cd Docking/

for i in {1..3};

do cd ERa-genistein/replication_$i/

for j in {1..1000};

do sort -n -k3rn -k2n dock_$j/filter_asp.csv | head -n1

>> filter_tc.csv

done

cd ../../

done

Lampiran 4. Script yang digunakan untuk menambatkan kembali OHT pada

REα

#!/bin/sh

alias plants='/home/enade/program/PLANTS/PLANTS1.2'

alias pyplif='/home/enade/.pyplif/pyplif.py'

mkdir -p Docking/ERa-OHT

cd Docking/

for i in $(seq 1 3);

do mkdir ERa-OHT/replication_$i

cd ERa-OHT/replication_$i

for j in $(seq 1 1000);

do mkdir dock_$j

cd dock_$j/

cp /home/kenny/Skripsi/Fileconfig/plants/plants.config2 .

cp /home/kenny/Skripsi/Fileconfig/plants/protein.mol2 .

cp /home/kenny/Skripsi/Fileconfig/plants/water.mol2 .

cp /home/kenny/Skripsi/Fileconfig/pyplif/config.txt .

cp /home/kenny/Skripsi/Fileconfig/pyplif/OHT.mol2 .

cp /home/kenny/Skripsi/Fileconfig/pyplif/ER_site.mol2 .

plants --mode screen plants.config2

pyplif

rm plants.config2 protein.mol2 water.mol2

config.txt ER_site.mol2 OHT.mol2

grep results pyplif.csv > nohead.csv

awk '{if(substr($4.103.1)=="1") {print

$1.$2.$3} else {print "N/A"}}' nohead.csv > filter_asp.csv

echo dock_$j >> ../docklist.txt

cd ../

done

cd ../../

done

Lampiran 5. Script yang digunakan untuk menghitung nilai RMSD OHT

Tc-PLIF filter

#!/bin/sh

for i in $(seq 1 3);

do mkdir -p Docking/ERa-OHT/analisis_hasil/replication_$i

cd Docking/ERa-OHT/analisis_hasil/replication_$i

cp ../../../../rmsd.OHT/rmsd.pml .

cp ../../../../rmsd.OHT/ref.pdb .

for j in $(seq 1 1000);

do cp

../../../ERa-OHT/replication_$i/dock_$j/nohead.csv .

awk '{if (substr($4.103.1)==1) print $0}' nohead.csv | awk

'{print $1"."$2"."$3}' | sort -t. -k3rn -k2n | head -n1 >

filter_tc.csv

awk -F. '{print "babel -d -imol2 dock"$1" -opdb

filtered.tcplif.pdb"}' filter_tc.csv > temp.sh

sed

"s/dock/..\/..\/..\/ERa-OHT\/replication_$i\/dock_$j\//g" temp.sh > convert.sh

chmod u+x convert.sh

./convert.sh

rm temp* filter_tc.csv convert.sh

mv filtered.tcplif.pdb filter_tcplif_$j.pdb

cp filter_tcplif_$j.pdb ligand.pdb

pymol -c rmsd.pml | grep "Executive" | awk '{print

$4}' > tmp

echo "$j `cat tmp`" >> rmsd.filter_tc.csv

rm tmp ligand.pdb

done

rm rmsd.pml ref.pdb

cd ../../../../

done

Lampiran 6. Script yang digunakan untuk menghitung nilai RMSD OHT

Tc-PLIF tanpa filtrasi

#!/bin/sh

for i in $(seq 1 3);

do mkdir -p Docking/ERa-OHT/analisis_hasil/replication_$i

cd Docking/ERa-OHT/analisis_hasil/replication_$i

cp ../../../../rmsd.OHT/rmsd.pml .

cp ../../../../rmsd.OHT/ref.pdb .

for j in $(seq 1 1000);

do cp

../../../ERa-OHT/replication_$i/dock_$j/nohead.csv .

awk '{print $1"."$2"."$3}' nohead.csv | sort -t. -k3rn -k2n

| head -n1 > nonfilter_tc.csv

awk -F. '{print "babel -d -imol2 dock"$1" -opdb

selected.tcplif.pdb"}' nonfilter_tc.csv > temp.sh

sed

"s/dock/..\/..\/..\/ERa-OHT\/replication_$i\/dock_$j\//g" temp.sh > convert.sh

chmod u+x convert.sh

./convert.sh

rm temp* nohead.csv nonfilter_tc.csv convert.sh

mv selected.tcplif.pdb nonfilter_tcplif_$j.pdb

cp nonfilter_tcplif_$j.pdb ligand.pdb

pymol -c rmsd.pml | grep "Executive" | awk '{print

$4}' > tmp

echo "$j `cat tmp`" >> rmsd.nonfilter_tc.csv

rm tmp ligand.pdb

done

rm rmsd.pml ref.pdb

cd ../../../../

done

Lampiran 7. Script yang digunakan untuk menghitung nilai RMSD OHT

ChemPLP filter

#!/bin/sh

for i in $(seq 1 3);

do mkdir -p Docking/ERa-OHT/analisis_hasil/replication_$i

cp rmsd.OHT/rmsd.pml

Docking/ERa-OHT/analisis_hasil/replication_$i

cp rmsd.OHT/ref.pdb

Docking/ERa-OHT/analisis_hasil/replication_$i

cd Docking/ERa-OHT/analisis_hasil/replication_$i

for j in $(seq 1 1000);

do cp

../../../ERa-OHT/replication_$i/dock_$j/nohead.csv .

awk '{if (substr($4.103.1)==1) print $0}' nohead.csv | awk

'{print $1"."$2"."$3}' | sort -t. -k2n -k3rn | head -n1 >

filter_chemplp.csv

awk -F. '{print "babel -d -imol2 dock"$1" -opdb

filtered.chemplp-pyplif.pdb"}' filter_chemplp.csv > temp.sh

sed

"s/dock/..\/..\/..\/ERa-OHT\/replication_$i\/dock_$j\//g" temp.sh > convert.sh

chmod u+x convert.sh

./convert.sh

rm temp* filter_chemplp.csv convert.sh

mv filtered.chemplp-pyplif.pdb filter_chemplp_$j.pdb

cp filter_chemplp_$j.pdb ligand.pdb

pymol -c rmsd.pml | grep "Executive" | awk '{print

$4}' > tmp

echo "$j `cat tmp`" >> rmsd.filter_chemplp.csv

rm tmp ligand.pdb

done

rm rmsd.pml ref.pdb

cd ../../../../

done

Lampiran 8. Script yang digunakan untuk menghitung nilai RMSD OHT

ChemPLP tanpa filtrasi

#!/bin/sh

for i in $(seq 1 3);

do mkdir -p Docking/ERa-OHT/analisis_hasil/replication_$i

cd Docking/ERa-OHT/analisis_hasil/replication_$i

cp ../../../../rmsd.OHT/rmsd.pml .

cp ../../../../rmsd.OHT/ref.pdb .

for j in $(seq 1 1000);

do cp

../../../ERa-OHT/replication_$i/dock_$j/nohead.csv .

awk '{print $1"."$2"."$3}' nohead.csv | sort -t. -k2n -k3rn

| head -n1 > nonfilter_chemplp.csv

awk -F. '{print "babel -d -imol2 dock"$1" -opdb

selected.chemplp-pyplif.pdb"}' nonfilter_chemplp.csv > temp.sh

sed

"s/dock/..\/..\/..\/ERa-OHT\/replication_$i\/dock_$j\//g" temp.sh > convert.sh

chmod u+x convert.sh

./convert.sh

rm temp* nohead.csv nonfilter_chemplp.csv convert.sh

mv selected.chemplp-pyplif.pdb

nonfilter_chemplp_$j.pdb

cp nonfilter_chemplp_$j.pdb ligand.pdb

pymol -c rmsd.pml | grep "Executive" | awk '{print

$4}' > tmp

echo "$j `cat tmp`" >> rmsd.nonfilter_chemplp.csv

rm tmp ligand.pdb

done

rm rmsd.pml ref.pdb

cd ../../../../

done

Lampiran 9. Script yang digunakan untuk menghitung nilai RMSD genistein

ChemPLP filter

#!/bin/sh

for i in $(seq 1 3);

do mkdir -p

Docking/ERa-genistein/analisis_hasil/replication_$i

cp rmsd.genistein/rmsd.pml

Docking/ERa-genistein/analisis_hasil/replication_$i

cp rmsd.genistein/ref.pdb

Docking/ERa-genistein/analisis_hasil/replication_$i

cd Docking/ERa-genistein/analisis_hasil/replication_$i

for j in $(seq 1 1000);

do cp

../../../ERa-genistein/replication_$i/dock_$j/nohead.csv .

awk '{if (substr($4.103.1)==1) print $0}' nohead.csv |

awk '{print $1"."$2"."$3}' | sort -t. -k2n -k3rn | head -n1

> filter_chemplp.csv

awk -F. '{print "babel -d -imol2 dock"$1" -opdb

filtered.chemplp-pyplif.pdb"}' filter_chemplp.csv > temp.sh

sed

"s/dock/..\/..\/..\/ERa-genistein\/replication_$i\/dock_$j\//g" temp.sh > convert.sh

chmod u+x convert.sh

./convert.sh

rm temp* filter_chemplp.csv convert.sh

mv filtered.chemplp-pyplif.pdb filter_chemplp_$j.pdb

cp filter_chemplp_$j.pdb ligand.pdb

pymol -c rmsd.pml | grep "Executive" | awk '{print

$4}' > tmp

echo "$j `cat tmp`" >> rmsd.filter_chemplp.csv

rm tmp ligand.pdb

done

rm rmsd.pml ref.pdb

cd ../../../../

done

BIOGRAFI PENULIS

Penulis skripsi dengan judul “Simulasi

Penambatan Molekuler Genistein pada Reseptor

Estrogen Alfa” memiliki nama lengkap Ricardo Kenny

Chandra. Penulis lahir di Lampung pada tanggal 4

Desember 1992 dari pasangan Gunawan dan Julina

sebagai anak pertama dari tiga bersaudara. Pendidikan

formal yang ditempuh penulis dimulai dari TK

Fransiskus Xaverius Tanjung Karang Lampung

(1996-1998), SD Fransiskus Xaverius Teluk Betung,

Lampung (1998-2004), SMP Mutiara Bangsa,

Tangerang (2004-2007), dan melanjutkan pendidikan

menengah atas di SMA Mutiara Bangsa (2007-2010).

Pada tahun 2010 penulis melanjutkan pendidikan ke jenjang Perguruan

Tinggi di Fakultas Farmasi Universitas Sanata Dharma Yogyakarta. Penulis

pernah menjadi anggota divisi pendamping kelompok Tiga Hari Temu Akrab

Farmasi (2011), koordinator divisi pendamping kelompok Tiga Hari Temu Akrab

Farmasi (2012), pengurus Komunitas Mahasiswa Buddhis dan Kong Hu Chu

koordinator divisi sosial periode 2012-2013. Penulis juga berperan aktif menjadi

asisten praktikum Kimia Analisis (2012), dan Analisis Farmasi (2013).