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Protein structure prediction:why
Protein No.
NOS1_RABIT 6 A K A T I L Y A T E T G K S Q A Y A KNOS3_HUMAN 7 A K A T I L Y G S E T G R A Q S Y A QNOS_RHOPR 8 A K A T I L F A T E T G K S E M Y A RNOS_ANOST 9 A K A T V L Y A T E T G R S E Q Y A RNOS_LYMST 10 A K C S I F Y A T E T G R S E R F A RNCPR_HUMAN 11 A N I I V F Y G S Q T G T A E E F A NNCPR_CANTR 12 A N T L L L F G S Q T G T A E D Y A N
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Predicting:• Expected quality of a model (QMode 1)• Expected error on residue Cα (QMode 2)
You may submit your quality assessment prediction in one of the two different modes:QMODE 1 : global model quality score (MQS - one number for a model)QMODE 2 : MQS and error estimate on per-residue basis.
Quoting the CASP web page:
Protein structure Quality prediction:The casp initiative
Target xx PredModel serv1_1 N1Model serv1_2 N2…………. …Model serv1_5 ……Model serv3_4 …….
Target yy PredModel serv1_1 N1Model serv1_2 N2…………. …Model serv1_5 ……Model serv3_4 …….
Target xx GDTModel serv1_1 G1Model serv1_2 G2…………. …Model serv1_5 ……Model serv3_4 …….
Target yy GDTModel serv1_1 G1Model serv1_2 G2…………. …Model serv1_5 ……Model serv3_4 …….
Protein structure Quality prediction:The casp initiative
Target xx PredModel serv1_1 N1Model serv1_2 N2…………. …Model serv1_5 ……Model serv3_4 …….
Target yy PredModel serv1_1 N1Model serv1_2 N2…………. …Model serv1_5 ……Model serv3_4 …….
Target xx GDTModel serv1_1 G1Model serv1_2 G2…………. …Model serv1_5 ……Model serv3_4 …….
Target yy GDTModel serv1_1 G1Model serv1_2 G2…………. …Model serv1_5 ……Model serv3_4 …….
Pearson correlation
By target
Protein structure Quality prediction:The casp initiative
Target xx PredModel serv1_1 N1Model serv1_2 N2…………. …Model serv1_5 ……Model serv3_4 …….
Target yy PredModel serv1_1 N1Model serv1_2 N2…………. …Model serv1_5 ……Model serv3_4 …….
Target xx GDTModel serv1_1 G1Model serv1_2 G2…………. …Model serv1_5 ……Model serv3_4 …….
Target yy GDTModel serv1_1 G1Model serv1_2 G2…………. …Model serv1_5 ……Model serv3_4 …….
Pearson correlation
Global
Protein structure Quality prediction:The casp initiative
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Cozzetto et al., Proteins 2007
Protein structure Quality prediction:The casp initiative
Protein structure modelling:A digression
Protein No.FLAV_CLOBE 1 A . . . I V Y W S G T G N T E K M A ECYSJ_THIRO 2 A . I T I L F G S Q T G N A K A V A E
…
Protein structure modelling:Expected accuracy
Cozzetto and Tramontano, Proteins 2004
Maistas: taking splicing into account
Protein No.FLAV_CLOBE 1 A . . . I V Y W S G T G N T E K M A ECYSJ_THIRO 2 A . I T I L F G S Q T G N A K A V A E
Protein No.FLAV_CLOBE 1 A . . . I V Y W S G T G N T E K M A E
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Maistas: taking splicing into account
http://www.bioinformatica.crs4.org
Maistas: taking splicing into account
ANTIBODIES: A different story
C
N
N C
H3 H1
H2L2
L1L3
V L
H2C
H1C
V H
H3C
V L
V H
H1C
H2C
H3C
C LC L
Antibody
Antigen binding site
SS
ANTIBODIES: A different story
ANTIBODIES: A different story
91 92 93 94 95 96 90 * *Y Q S L P Y Q
91 92 93 94 95 96 90 * *W T Y P L I Q
95Pro
90Gln
94Pro
ANTIBODIES: A different story
Chothia et al., Nature 1989
Canonical structures for the ‘torso’ of H3:94R – 101D
94 non R or 101 non D
103
94101
103
94101
Morea et al., JMB., 1998
ANTIBODIES: A different story
target sequence
BLAST
Align
VL templateTL
Build framework
ANTIBODIES: A different story
ANTIBODIES: A different story
target sequence
Build framework
Align
BLAST
VL templateTL
target sequence
BLAST
Align
template
Build framework
ANTIBODIES: A different story
Ab VL sequence Ab VH sequence
“BLAST”
VL templateTL
VH templateTH
“Align”
TL=TH?
Fit conserved interface
Build template
Build framework
“Align”
Ab VL sequence Ab VH sequence
“BLAST”
VL templateTL
VH templateTH
TL=TH?
Fit conserved interface
Build template
Build framework
ANTIBODIES: A different story
Taking the frameworks from different structures introduces errors
One might be better off selecting the same template, at the cost of loosing in sequence identity
ANTIBODIES: A different story
Taking the loops from different structures introduces errors
One might be better off selecting a template with the right CS, at the cost of loosing in sequence identity
ANTIBODIES: A different story
•Same antibody•Same antibody and canonical structures •Same canonical structures•Best Vl and Vh
ANTIBODIES: A different story
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ANTIBODIES: A different story
?
ANTIBODIES: A different story
ANTIBODIES: A different story
AVACFATGAFGTARASDFEARTASADFAERAYHGTARYAPLSVNTERAT…..
ADFAERAYLDFNMRSYPDFHGRTYAEFKLLSY
ANTIBODIES: A different story
ANTIBODIES: A different story
ANTIBODIES: A different story
ANTIBODIES: A different story
ANTIBODIES: A different story
ANTIBODIES: A different story
PDB
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ANTIBODIES: A different story
ANTIBODIES: A different story
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ANTIBODIES: A different story
?
acknowledgements
Giuliana BrunettiEnrico Capobianco Simone CarcangiuAlberto de la FuenteMatteo Floris Elisabetta MarrasJoël MasciocchiElisabetta MuscasMassimiliano OrsiniEnrico PieroniFrédéric ReinierPatricia Rodriguez Tome’Alphonse Thanaraj ThangavelMaria Valentini
Tiziana CastrignanòP. D’Onorio De Meo Danilo Carrabino
Domenico Cozzetto Enrico FerraroFabrizio Ferre’Emanuela GiombiniAlejandro Giorgetti Paolo MarcatiliDomenico RaimondoStefania Bosi
Claudia BertonatiAlessandra GodiMichele CerianiRomina OlivaClaudia BonacciniMarialuisa Pellegrini Simonetta Soro
EU Biosapiens Institut Pasteur-Cenci
HFPRegione Sardegna
EU Biosapiens Institut Pasteur-Cenci
HFPRegione Sardegna
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8
8th
Cagliari, SardiniaItaly
Sometimes early December 2008