Protein modelling

http://biome.ngic.re.kr/ProteinModelling/

Problem (문제정의)

• Build 3D structural models of given or interested proteins
  • Initial input: amino acid sequence of the target protein
  • Final output: its predicted 3D structure

Method

• Find one or more structural templates of the target protein via sequence homology search against known structures (program: BLASTP or PSI-BLAST, database: PDB)

• Download template structures in PDB format (web server: RCSB PDB)
• Align the amino acid sequence of the target protein with that(those) of the template protein(s) (program: CLUSTALW, output: PIR format)
• Build 3D structural models based on the multiple sequence alignment and the template 3D structure(s) (program: MODELLER, input: ATM, ALI, and TOP files)
  • manual build
    • manually convert file formats from PDB to ATM and PIR to ALI, respectively
    • write a TOP script file
    • run MODELLER
  • automatic build (some PDB and PIR files are not successfully converted to correct ATM and ALI files due to amino-acid sequence mismatch)
    • perl script to generate ATM, ALI, and TOP files from PDB and PIR files: txt, gz
    • command-line arguments in order: base_directory_path pir_file_name target_protein_id(exactly 4 letters) one_or_more_PDB_file_names(exactly 4-letter prefix)
    • run the perl script (e.g. ../bin/makeModellerInput.pl /home/user/Protein3DModelling/KCIP KCIP.pir KCIP 1QJA.pdb)
    • run MODELLER (e.g. mod7v7 KCIP.top)
  • example
    • ATM file: 5fd1.atm
    • ALI file: alignment.ali
    • TOP file: model-default.top
    • command: mod7v7 model-default.top
    • output PDB file (predicted model): 1fdx.B99990001.pdb
  • MODELLER manual
    • PDF, HTML
• Display and compare the 3D structures of the model and the template proteins (program: RasMol)

Sample proteins (단백질 예제들)

• Sample protein A: 14-3-3 protein gamma (Protein kinase C inhibitor protein-1; KCIP-1)

>sw|P61981|143G_HUMAN 14-3-3 protein gamma (Protein kinase C inhibitor protein-1) (KCIP-1) VDREQLVQKARLAEQAERYDDMAAAMKNVTELNEPLSNEERNLLSVAYKNVVGARRSSWR VISSIEQKTSADGNEKKIEMVRAYREKIEKELEAVCQDVLSLLDNYLIKNCSETQYESKV FYLKMKGDYYRYLAEVATGEKRATVVESSEKAYSEAHEISKEHMQPTHPIRLGLALNYSV FYYEIQNAPEQACHLAKTAFDDAIAELDTLNEDSYKDSTLIMQLLRDNLTLWTSDQQDDD GGEGNN

• Sample protein B: GAK_HUMAN Cyclin G-associated kinase (GAKH)

>sw|O14976|GAK_HUMAN Cyclin G-associated kinase MSLLQSALDFLAGPGSLGGASGRDQSDFVGQTVELGELRLRVRRVLAEGGFAFVYEAQDV GSGREYALKRLLSNEEEKNRAIIQEVCFMKKLSGHPNIVQFCSAASIGKEESDTGQAEFL LLTELCKGQLVEFLKKMESRGPLSCDTVLKIFYQTCRAVQHMHRQKPPIIHRDLKVENLL LSNQGTIKLCDFGSATTISHYPDYSWSAQRRALVEEEITRNTTPMYRTPEIIDLYSNFPI GEKQDIWALGCILYLLCFRQHPFEDGAKLRIVNGKYSIPPHDTQYTVFHSLIRAMLQVNP EERLSIAEVVHQLQEIAAARNVNPKSPITELLEQNGGYGSATLSRGPPPPVGPAGSGYSG GLALAEYDQPYGGFLDILRGGTERLFTNLKDTSSKVIQSVANYAKGDLDISYITSRIAVM SFPAEGVESALKNNIEDVRLFLDSKHPGHYAVYNLSPRTYRPSRFHNRVSECGWAARRAP HLHTLYNICRNMHAWLRQDHKNVCVVHCMDGRAASAVAVCSFLCFCRLFSTAEAAVYMFS MKRCPPGIWPSHKRYIEYMCDMVAEEPITPHSKPILVRAVVMTPVPLFSKQRSGCRPFCE VYVGDERVASTSQEYDKMRDFKIEDGKAVIPLGVTVQGDVLIVIYHARSTLGGRLQAKMA SMKMFQIQFHTGFVPRNATTVKFAKYDLDACDIQEKYPDLFQVNLEVEVEPRDRPSREAP PWENSSMRGLNPKILFSSREEQQDILSKFGKPELPRQPGSTAQYDAGAGSPEAEPTDSDS PPSSSADASRFLHTLDWQEEKEAETGAENASSKESESALMEDRDESEVSDEGGSPISSEG QEPRADPEPPGLAAGLVQQDLVFEVETPAVLPEPVPQEDGVDLLGLHSEVGAGPAVPPQA CKAPSSNTDLLSCLLGPPEAASQGPPEDLLSEDPLLLASPAPPLSVQSTPRGGPPAAADP FGPLLPSSGNNSQPCSNPDLFGEFLNSDSVTVPPSFPSAHSAPPPSCSADFLHLGDLPGE PSKMTASSSNPDLLGGWAAWTETAASAVAPTPATEGPLFSPGGQPAPCGSQASWTKSQNP DPFADLGDLSSGLQGSPAGFPPGGFIPKTATTPKGSSSWQTSRPPAQGASWPPQAKPPPK ACTQPRPNYASNFSVIGAREERGVRAPSFAQKPKVSENDFEDLLSNQGFSSRSDKKGPKT IAEMRKQDLAKDTDPLKLKLLDWIEGKERNIRALLSTLHTVLWDGESRWTPVGMADLVAP EQVKKHYRRAVLAVHPDKAAGQPYEQHAKMIFMELNDAWSEFENQGSRPLF