“LAPORAN PRAKTIKUM” “MOLEKULAR DOCKING DENGAN APLIKASI AUTODOCK VINA” A. TUJUAN 1. Mempre Mempredik diksi si se! se!"#" "#" d"ri d"ri s$"%$ s$"%$ &'"%. &'"%. (. E)ek%i*i%"s E)ek%i*i%"s me%&de me%&de M&+e,$+"r M&+e,$+"r D&,kiD&,ki- "$%&d&ks "$%&d&ks Vi". Vi". /. DASA DASAR R TEOR TEORII Perk Perkem em'" '"-" " i+m$ i+m$ pepe-e%" e%"0$ 0$" " d" d" %ek %ek&+ &+&&-ii p"d" p"d" "m" "m" ii ii d"p"% d"p"% mem'"%$ me2"#"' d" me2e+"sk" 'er'"-"i m","m )e&me" s"is !"- %er2"di diseki%"r diseki%"r ki%". /e-i%$ /e-i%$ p$ di 'id"'id"- kimi" )"rm"si !"- sem"ki sem"ki 'erkem'"'erkem'"- d"+"m peem$" d" per","-" &'"% '"r$ !"- +e'i0 '"ik e)ik"si!" d" memiim"+isir e)ek s"mpi- !"- %er2"di. Di er" m&der ii me%&de pe-em'"-" &'"% 3 &'"%" s$d"0 s$d"0 m$+"i m$+"i m"s$k m"s$k ke r""0 r""0 i+m$ i+m$ k&mp$% k&mp$%"si "si d"+"m d"+"m mem"0"m mem"0"mii s%r$k%$ s%r$k%$rr 'i&+&'i&+&-ii m&+ek$+er d" peem$" &'"% 'erd"s"rk" s%r$k%$r. 4"+ ii dise'$% 5Computer 5 Computer aided drug design6 design6 7des"i &'"% 'er'"%$ k&mp$%er8. S"+"0 s"%$ me%&de !"- di-$"k" "d"+"0 Molecular "d"+"0 Molecular Docking . Se," Se,"r" r" '"0" '"0"s" s" 5m&+ 5m&+e, e,$+ $+"r "r66 'er" 'er"r% r%ii
m&+e m&+ek$ k$+e +er r d" d"
5d&, 5d&,ki ki-66 'er" 'er"r% r%ii
pe"m'"%" se0i--" d"p"% di"r%ik" 5pe"m'"%" m&+ek$+er6. D"+"m 0"+ ii !"di%"m'"%k" "d"+"0 m&+ek$+ &'"% 7+i-"8 p"d" resep%&r!" 7%"r-e% &'"%8. M&+ek$+ &'"% ii d"p"% 'er$p" se!"#" !"- diprediksi memi+iki "k%i*i%"s )"rm"k&+&-is '"ik i%$ se!"#" d"ri eks%r"k %$m'$0" "%"$p$ se!"#" si%esis.
Docking di-$"k" $%$k me-e%"0$i '"-"im"" +i-" 'eri%er"ksi de-" si%$s si%$s %"m'"% %"m'"% resep%& resep%&r! r!"" se0ise0i--" -" d"p"% d"p"% dipred diprediks iksii "k%i)i% "k%i)i%"s! "s!". ". Li-" Li-" 'i"s"! 'i"s"!"" 'er$p" m&+ek$+ ke,i+ "%"$ d"p"% p$+" 'er$p" pr&%ei. Sed"-" resep%&r 'er$p" r"-k"i" s$s$" "s"m "mi& pr&%ei "%"$ d"p"% p$+" 'er$p" DNA "%"$ RNA !"%erd"p"% d"+"m se+ %$'$0.
Docking "d"+"0 me%&de $%$k memprediksi &rie%"si !"- %er'"ik d"ri s$"%$ m&+ek$+ ke%ik" %erik"% s"%$ s"m" +"i $%$k mem'e%$k k&mp+eks !"- s%"'i+. I)&rm"si %e%"- &rei%"si ii d"p"% di-$"k" $%$k memprediksi kek$"%" 0$'$-" "%"$ ")ii%"s "%"r" d$" m&+ek$+ !"- di-$"k". AutoDock Vina "d"+"0 s"+"0 s"%$ pir"%i +$"k docking, dir","- $%$k memprediksik" '"-"im"" m&+ek$+9m&+ek$+ ke,i+ seper%i i0i'i%&r %erik"% p"d" resep%&r d"+"m 'e%$k s%r$k%$r :D. P"d" d"s"r!" AutoDock Vina %erdiri d"ri d$" pr&-r"m $%"m" !"i%$ AutoDock !"- mem'"%$ pr&ses docking d"ri ligand ke sek$mp$+" grids !"- mediskripsik" pr&%ei !"- di%$2$ AutoGrid !"mem'"%$ per0i%$-" grids %erse'$%. 4"+ ii d"p"% di-$"k" se'"-"i ped&m" d"+"m per","-" s%r$k%$r kimi" "-"r diper&+e0 ik"%" !"- +e'i0 '"ik +"-i. U%$k me+"k$k" ke-i"%" Molecular Docking de-" Autodock Vina, diper+$k" 'e'er"p" "p+ik"si seper%i 'erik$%;
9
Autodock Vina 7Di-$"k" $%$k me+"k$k" pr&ses Molecular Docking 8
9 DS Visualizer 7U%$k prep"r"si resep%&r %"r-e% d" +i-"d !"- "k" di$2i d"p"% 2$-" di-$"k" $%$k *is$"+is"si 0"si+ Molecular Docking 8 9 MGLTools "%"$ AutodockTools 7Di-$"k" $%$k me-&+"0 resep%&r %"r-e% d" +i-"d $2i "-"r d"p"% dieksek$si &+e0 "p+ik"si Autodock Vina "p+ik"si ii 2$-" d"p"% di-$"k" $%$k me!i"pk" p"r"me%er9p"r"me%er d&,ki-8 9 Python 7Ap+ik"si !"- di-$"k" $%$k me2"+"k" "p+ik"si9"p+ik"si !"- p"d" $m$m!" di'$"% de-" me--$"k" '"0"s" pemr&-r"m" Python s"+"0 s"%$!" "d"+"0 MGLTools8 9
ASA!A 7D"p"% di-$"k" $%$k prep"r"si resep%&r %"r-e% d" +i-"d $2i "m$ p"d" ke-i"%" ii di-$"k" $%$k me-$k$r i+"i RMSD8
9
"pen #a$el 7Ap+ik"sik" !"- di-$"k" $%$k me-k&*ersi 0"si+ d&,ki- d"ri )&rm"% PD/
C. ALAT DAN /A4AN 1. A+"% 9 Seper"-k"% pers&"+ ,&mp$%er 9 S&)%#"re ; A$%&d&,ks Vi" Dis,&*er! S%$di& Vis$"+ier A$%&d&,kT&&+s Ope /"'e+ P0!%& (. /"0" 9 Resep%&r ; *ir$s 4IV k&de 14SG 9 U2i se!"#" &'"% Idi"*ir D. CARA KERJA ". Pengunduhan Reseptor Target 1. "p+ik"si $ro%ser 7seper%i Google Chrome, Mozila &ire'o(, )C #ro%ser, dan se$againya8 (. K$2$-i link ###.r,s'.&r:. Ke%ik k&de resep%&r "%"$ "m" resep%&r !"- dii-ik" p"d" %&m'&+ Search. Se'"-"i ,&%&0 ke%ik k&de 1HSG "k" did"p"%k" se'$"0 resep%&r 'er$p" 'e%$k kris%"+ d"ri *ir$s 4IV di+e-k"pi +i-"d "s+i 7nati*e ligand 8 'er$p" se!"#" &'"% Indinavir =. K+ik %&m'&+ download files $%$k me-$d$0 resep%&r %erse'$% d" pi+i0 PDB Format $%$k med"p"%k" resep%&r $2i de-" )&rm"% PD/
'. Preparasi Reseptor Target dan Ligand Uji 1. /$k" "p+ik"si DS Visualizer k+ik File !pen (. Pi+i0 resep%&r 1HSG k+ik !pen :. Tek" %&m'&+ "TRL#H$ 0"p$s sem$" +i-"d !"- "d" p"d" resep%&r %erse'$% p"s%ik" 2$-" 'e'"s d"ri m&+ek$+ "ir 0em&-+&'i d" se'"-"i!". =. Simp" resep%&r !"- s$d"0 diprep"r"si de-" ,"r" k+ik File Save %s& Simp" de-" )&rm"% PD/ d" %ek" %&m'&+ Save& >. U%$k prep"r"si +i-"d "s+i se'"-"i +i-"d $2i !pen +"-i 'ile 14SG de-" me--$"k" "p+ik"si DS Visualizer
,. 'onversi File Reseptor dan Ligand dalam Bentu( PDB)T 1. J"+"k" "p+ik"si Autodock Tools +-. !"- s$d"0 %ersedi" di desk%&p (. K+ik %&m'&+ !pen$ kem$di" pi+i0 )i+e resep%&r !"- s$d"0 diprep"r"si. Kem$di" k+ik !pen&
:. Se%e+"0 i%$ %"m'"0k" "%&m 4!dr&-e p"d" resep%&r $2i k+ik H*drogens %dd Polar !nl* !'
=. Kem$di" simp" resep%&r $2i d"+"m 'e%$k PD/. k+ik Grid +a,romole,ule "hoose 'li( nama reseptorn*a -1HSG. Sele,t +ole,ule Beri nama /ile 01hsg&pd2t3 Save
?. Kem$di" "%$r -rid 7'"-i" resid$ !"- m"" s"2" !"- i-i di2"dik" s"s"r" +i-"d $%$k 'eri%er"ksi8 k+ik Grid Grid Bo4&& %tur u(uran o4 seperti pada gamar 'li( File "lose Saving "urrent
@. Se%e+"0 i%$ k&*ersi )i+e +i-"d ke d"+"m 'e%$k PD/
. Kem$di" k+ik Ligand Torsion Tree Set 5umer o/ Torsion pasti(an nilain*a ma(simum Dismiss
B. 'li( Ligand !utput Save %s PDB)T Beri nama 0ligand&pd2t3 Save
d. +ole,ular Do,(ing dengan %utodo,( 6ina P"s%ik" )i+e reseptor&pd2t d" ligand&pd2t 'er"d" p"d" )&+der !"- s"m" !"i%$ p"d" Drive "7 6ina& 1. /$"% )i+e te4t '"r$ 7K+ik k"" p"d" #ids ep+&rer Ne# 7Te% D&,$me%8 'eri "m" ,on/&t4t (. Isik" )&rm p"d" -"m'"r 'erik
%$ :. "ommand Prompt 8indo9s de-" ,"r" k+ik Start 'eti( RU5 "%"$ 'is" 2$-" de-" meek" %&m'&+ Bendera 8indo9s # R$ kem$di" k+ik "+D :nter
=. Se%e+"0 i%$ p"d" "ommand Prompt ke%ik k&de seper%i !"- "d" p"d" -"m'"r
>. T$--$ s"mp"i pr&ses!" se+es"i. Se%e+"0 se+es"i $%$k mem$d"0k" *is$"+is"si pe,"0 )i+e output&pd2t me2"di )i+e %erpis"0 p"d" m"si-9m"sik&)&rm"si!". C"r"!" ke%ik k&de p"d" -"m'"r di "ommand Prompt :nter
?. P"d" )&+der vina "k" m$,$+ 'e'er"p" )i+e k&)&rm"si 0"si+ d&,ki- se0i--" +e'i0 m$d"0 $%$k di""+isis d" di*is$"+is"si e. Vis$"+is"si 0"si+ d&,ki1. /$k" "p+ik"si Ope /"'e+ (. Pi+i0 k&)&rm"si !"- "k" di*is$"+is"si :. P"d" '"-i" ip$% pi+i0 )&rm"% )i+e !"- "k" dik&*ersi 7PD/. K+ik T&m'&+ "onvert ?. Se%e+"0 did"p"%k" )i+e PD/ '$k" )i+e 1hsg&pd de-" "p+ik"si DS Visualizer @. K+ik File Insert From File; hasil do,(ing -out
. K+ik me$ Re,eptor>Ligand Intera,tion B. Tek" %&m'&+ "trl#H 'li( ligand hasil do,(ing K+ik De/ine Ligand Se%e+"0 i%$ k+ik Ligand Intera,tion 1. ,"r" (li( (anan pada agian a,(ground "olor Ba,(ground %tur 9arna menjadi putih
11. (li( (anan pada a,(ground (li( Laels %dd&& pada !je,t pilih %mino %,id U(uran Font 1? 8arna Hitam !'
E. DATA PENGAMATAN Pr&%ei !"- di-$"k" "d"+"0 pr&%ei 14SG !"- mer$p"k" resep%&r 'e%$k kris%"+ !"- 'er"s"+ d"ri *ir$s 4IV di+e-k"pi +i-"d "s+i 'er$p" se!"#" &'"% idi"*ir.
Se%e+"0 pr&ses d&,ki- di+"k$k" ses$"i de-"" ,"r" ker2" m"k" se+"2$%!" di ""+isis i+"i RMSG de-" pr&-r"m ,&mm"d pr&m%. Ii "d"+"0 0"si+ d"ri -ird p"d" "$%&d&,k %&&+s !"- di-$"k" $%$k ""+isis i+"i RMSG !"i%$ i+"i SIHE d" CENTER 7!8
D"%" %erse'$% kem$di" dim"s$kk" ked"+"m %e% 7,&).%%8
Hasil 7 Dari gamar diatas merupa(an analisis nilai dari RS+G do,(ing 1 HSG antar ligand dan protein& Tapi pada per,oaan *ang (ami la(u(an terjadi (esalahan dalam prosedur sehingga :RR!R&
. PEM/A4ASAN P"d" pr"k%ik$m k"+i ii di-$"k" *ir$s 4IV se'"-"i resep%&r d" idi"*ir se'"-"i se!"#" $2i. D&,ki- m&+e,$+"r di+"k$k" de-" me--$"k" "p+ik"si A$%&d,ks Vi". T$2$" d"ri pr"k%ik$m ii "d"+"0 memprediksi ik"%" se!"#" &'"% de-" resep%&r d" e)ek%i*i%"s me%&de M&+e,$+"r D&,ki- "$%&d&ks Vi". Se!"#" &'"% d"p"% di d+&"d p"d" -$d"- -e di si%$s ###.r,s'.&r-. A,F$ired Imm$e De)i,ie,! S!dr&me 7AIDS8 mer$p"k" k$mp$+" -e2"+" pe!"ki% !"- dise'"'k" &+e0 4$m" Imm$&de)i,ie,! Vir$s 74IV8. Sese&r"- !"%eri)eksi *ir$s 4IV "%"$ mederi%" AIDS seri- dise'$% de-" Od0" si-k"%" d"ri &r"- !"- 0id$p de-" 4IVAIDS. Pederi%" i)eksi 4IV di!"%"k" se'"-"i pederi%" AIDS ke%ik" me$2$kk" -e2"+" "%"$ pe!"ki% %er%e%$ !"- mer$p"k" "ki'"% pe$r$" d"!" %"0" %$'$0 !"- dise'"'k" *ir$s 4IV.
Vir$s 4IV mer$p"k" re%r&*ir$s !"- %erm"s$k -&+&-" *ir$s RNA 7*ir$s !"me--$"k" RNA se'"-"i m&+ek$+ pem'"#" i)&rm"si -ee%ik8. Dise'$% re%r&*ir$s k"re" memi+iki eim re*erse %r"s,rip%"se. Eim ii mem$-kik" *ir$s me-$'"0 i)&rm"si -ee%ik!" !"- 'er"d" d"+"m RNA ke d"+"m 'e%$k DNA !"- kem$di" dii%e-r"sik" ke d"+"m i)&rm"si -ee%ik se+ +im)&si% !"- diser"-. De-" demiki" 4IV d"p"% mem")""%k" mek"isme se+ +im)&si% $%$k me-k&pi diri!" me2"di *ir$s '"r$ !"- memi+iki ,iri9,iri 4IV. 4IV me!er"- sis%em im$ m"$si" !"i%$ me!er"+im)&si% T 0e+per !"- memi+iki resep%&r CD= di perm$k""!". Lim)&si% T 0e+per "%"r" +"i 'er)$-si me-0"si+k" "% kimi" !"- 'erper" se'"-"i per"-s"- per%$m'$0" d" pem'e%$k" se+9se+ +"i d"+"m sis%em im$ d" pem'e%$k" "%i'&di se0i--" !"- %er-"--$ '$k" 0"!" )$-si +im)&si% T %e%"pi 2$-" +im)&si% / m&&si% m"kr&)"d" se'"-"i!". Idi"*ir "d"+"0 i0i'i%&r p&%e d"ri eim pr&%e"se 4IV !"- dip"k"i d"+"m rep+ik"si
*ir$s
!"- me-"ki'"%k" AIDS. Pr&%e"se i0i'i%&r
'eker2"
de-"
me&"k%i)k" eim pr&%e"se !"- $%"m" $%$k rep+ik"si d"ri *ir$s AIDS. U2i k+iis s$d"0 %$2$kk" '"0#"s"!" idi"*ir !"- me"m'"0 s!s%em keke'"+" '"d" de-" me"m'"0 2$m+"0 se+ CD= ser%" me-0impi% 2$m+"0 *ir$s !"- 'ered"r d"+"m "+ir" d"r"0. D"mp"k "%i*ir$s pe%i- idii*ir s$d"0 diper+i0"%k" me+e#"%i %i-k"% pe$r$" "%i-e p(= !"- dip"k"i $%$k me-$k$r %i-k"% 4IV d"+"m d"r"0. Idii*ir
2$-" s$d"0 diper+i0"%k" $%$k me"m'"0 kem"mp$" s!s%em keke'"+" '"d" de-" me"m'"0 2$m+"0 CD=.
Gamar 1 Sen*a9a Indinavir
Pr&%e"se "d"+"0 eim !"- me-0idr&+isis ik"%" pep%ide p"d" m&+ek$+ pr&%ei !"- me-0"si+k" pep%ide "%"$ "s"m "mi&. Pr&%ei %erdiri "%"s m&+ek$+ "s"m "mi& !"- 'er*"ri"si 2$m+"0!" 'erkis"r "%"r" 1 s"mp"i ri'$" !"- 'er)$-si se'"-"i $i% pe!$s$ p&+imer pr&%ei !"- %er"-k"i me+"+$i ik"%" pep%id". Pr&%ei !"- memi+iki +e'i0 d"ri 1 "s"m "mi& dise'$% p&+ipep%id" sed"-k" is%i+"0 pr&%ei di%$2$k" '"-i p&+imer "s"m "mi& de-" 2$m+"0 di "%"s 1 7S$0"r%&&1BB8. Se'e+$m d&,ki- m&+e,$+"r di+"k$k" prep"r"si pr&%ei d" +i-" %er+e'i0 d"0$+$. Prep"r"si pr&%ei d" +i-" di-$"k" $%$k mempersi"pk" se'e+$m di-$"k" $%$k d&,ki-. Pr&%ei %"r-e% !"- di-$"k" d"+"m pr&ses d&,ki- mer$p"k" pr&%ei 0"si+ d"ri 9R"! !"- di"m'i+ d"ri d"%" '"k se!"#" &'"% $%$k pr&%ei =RS de-" "+"m"% 0%%p;pd'.&r-. 4"si+ d"ri prep"r"si ii "d"+"0 pr&%ei %"p" +i-". Prep"r"si pr&%ei d" +i-" di+"k$k" +"-s$- me--$"k" s&)%#"re P!R9A$%&d&,kVi". Pr&%ei !"- %e+"0 diprep"r"si me-"+"mi ke0i+"-" "ir 74(O8 !"- %id"k 'eri%er"ksi de-" DRO. 4"si+ prep"r"si pr&%ei =RS di""+isis me--$"k" )i%$r A$%&d&ks%&&+. S%"'i+i%"s 'e%$k -e&me%ri :D $r$%" "s"m "mi& d"ri pr&%ei !"- di%$2$kk" &+e0 %i%ik9%i%ik 0i%"m 7me#"ki+i s"%$resid$ "s"m "mi&8 !"- 'er"d" di d"+"m "re" k$r*" sed"-k" 'e%$k d" p&sisi -e&me%ri :D !"- %id"k s%"'i+ di%"d"i de-" %i%ik9%i%ik 0i%"m !"- 'er"d" di +$"r "re" k$r*". Se%e+"0 pr&%ei d" +i-" diprep"r"si kem$di" di+"k$k" pe!"%$" "%"r" pr&%ei de-" +i-" me--$"k" "p+ik"si A$%&d&ks%&&+ d" p"s%ik" pe!"%$" %erse'$% m"s$k ke d"+"m -rid '&. Pe-"%$r" -rid '& ii 'er%$2$" me-"r"0k" +i-" se!"#" &'"% idi"*ir $%$k 'eri%er"ksi p"d" d"er"0 di d"+"m resep%&r.
Ni+"i kedek"%" s%r$k%$r +i-" se'e+$m d" se%e+"0 di+"k$k" d&,ki- m&+e,$+"r me--$"k" p"r"me%er RMSD 7R&&%9Me"9SF$"re De*i"%i&8 de-" me--$"k" pr&-r"m C&mm"d Pr&mp. 4"si+ RMSD k$r"- d"ri ( me$2$k" me%&de %erse'$% d"p"% di-$"k" Ide%i)ik"si 4"si+ D&,ki- Li-" U2i. RMSD 7R&&% Me" SF$"re De*i"%i&8 "d"+"0 p"r"me%er !"- di-$"k" $%$k me-e*"+$"si kemirip" d$" '$"0 s%r$k%$r. Kemirip" %erse'$% di$k$r 'ed"s"rk" per'ed"" 2"r"k "%&m se2eis. Ni+"i RMSD !"- diper&+e0 d"ri resep%&r de-" k&de =RS "d"+"0 1B=>@. Se%e+"0 did"p"% RMSD ( m"k" di+"k$k" pr&ses d&,ki- p"d" resep%&r %erse'$%. Se%e+"0 dike%"0$i i+"i RMSD ( m"k" dipi+i0 )i+e kem$di" dim"s$kk" ke d"+"m )&+der d&,ki- d" ,&*er% )i+e d"ri pd'F% ke pd' me+"+$i "p+ik"si Ope /"'e+. Ter"k0ir +i0"% 0"si+ d&,ki- m&+e,$+"r me--$"k" DS Vis$"+ier. U%$k memper2e+"s ik"%" resep%&r de-" +i-" d"p"% di+"k$k" per$'"0" #"r" p"d" '",k-r&$d.
Ke+e'i0" me%&de pem&de+" m&+ek$+ 7molecular docking 8 "d"+"0 d"p"% di-$"k" $%$k memprediksi "k%i*i%"s s$"%$ se!"#" se'e+$m di+"k$k" si%esis se0i--" me-$r"-i pe--$"" pe+"r$% d" '"0"'"0" kimi" !"- d"p"% me,em"ri +i-k$-".
P"d" pr"k%ik$m k"+i ii %er2"di err&r ke%ik" "k" me+"k$k" ""+isis i+"i RMSD dik"re"k" 'e'er"p" 0"+ !"i%$ ; 1. Kes"+"0" pr"k%ik" d"+"m pe!imp"" )i+e prep"r"si pr&%ei d"+"m %emp"% !"- 'e"r (. i+e p"d" ,&mm"d pr&mp !"- dim"s$kk" %id"k ses$"i de-" )i+e !"disimp" &+e0 pr"k%ik" :. Ter+e#"% 'e'er"p" +"-k"0 pe-er2"" "ki'"% k$r"-!" ke%e+i%i" d"ri pr"k%ik" Kek$r"-" d" ke+e'i0" d"ri m"si-9m"si- Ap+ik"si ; 1. %utodo,( 6ina ; Ke+e'i0" d"ri pr&-r"m AutoDock Vina "d"+"0 m$d"0 di-$"k" pr&-r"m %id"k 'er'"!"r ,ep"% repr&d$si'e+ d" multiple CPU s/Cores. Sed"-k" kek$r"-" d"ri pr&-r"m AutoDock Vina "d"+"0 %id"k d"p"% mempr&ses docking de-" m&+ek$+ $k$r" 'es"r %id"k d"p"% me+"k$k" docking %"p" s%r$k%$r %i-" dimesi d" %id"k d"p"% me+i0"% i%er"ksi "%"r" pr&%ei de-" pr&%ei. (. DS 6isuali@er 7 ke+e'i0"!" !"i%$ m$d"0 di -$"k" pr&-r"m %id"k 'er'"!"r. Kek$r"-"!" "d"+"0 )&rm"% )i+e !"- di-$"k" 0"r$s %ep"%. J ik" %id"k m$d"0 %er2"di err&r.
:. %utodo,( Tools 7 de-" "p+ik"si ii ki%" d"p"% mer"m"+k" s$'s%r"% !"- p"+i,&,&k $%$k me-isi sisi "k%i) s$"%$ se!"#". =& !pen Bael 7 ke+e'i0"!" d"p"% me-k&*ersi )i+e de-" 'er'"-"i m","m eks%esi d"p"% di-$"k" se,"r" m$+%ip+e
G. KESIMPULAN /erd"s"rk" pr"k%ik$m !"- %e+"0 di+"k$k" d"p"% di di"m'i+ simp$+"; 1. De-" Me%&de d&,ki- !"- di+"k$k" de-" "p+ik"si !"i%$ "$%&d&,k *i" DS Vis$"+ier A$%&d&,k T&&+s Ope /"'e+ d"p"% di+"k$k" prediksi i%er"ksi se!"#" idi"*ir 7+i-"d8 de-" *ir$s 4IV 7resep%&r8. (. Ap+ik"si D&,ki- s"-"% e)ek%i) d"+"m me+"k$k" m&+ek$+"r d&,ki- "%"r" +i-"d de-" resep%&r. :. De-" "p+ik"si ii d"p"% mer"m"+k" s$'s%r"% !"- p"+i- ,&,&k $%$k me-isi sisi "k%i) s$"%$ se!"#". 4. DATAR PUSTAKA A&im (1? M&d$+ /i&+&-i M&+ek$+er /+&k 11 Pr&-r"m S%$di "rm"si. • •
•
UM. A&im. “ke+e'i0" d&,ki-”. ( Apri+ (1?. 0%%p;epri%s.$s.",.id(=?>:G1(:1'"'(.pd) A#"+$ddi ikri.” Me-e"+ M&+e,$+"r D&,ki- 7Pe"m'"%" M&+ek$+8”. ( Apri+
(1?.
0%%p;ri,k!ri,0m&s+em.'+&-sp&%.,&.id(1>1me-e"+9
m&+e,$+"r9d&,ki-9pe"m'"%".0%m+ •
I.
LAMPIRAN
4"si+ A"+isis i+"i RMSG !"- se0"r$s!" seper%i p"d" -"m'"r di"%"s.
Ii mer$p"k" 0"si+ d&,ki- !"- di+i0"% "#" e+ek%r& !"i%$ d&&r pr&%& d" ",,ep%&r pr&%&