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PSSJ 2016-06-07
Application of the integrated NMR database in protein science
Naohiro Kobayashi
PDBj-BMRB group Institute for Protein Research
Osaka university, Japan
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PSSJ 2016-06-07
NBDC
wwPDB
Project director Haruki Nakamura
PDBj: Database for X-ray and EM structure
and experimental data Haruki Nakamura (Professor)
Atsushi Nakagawa (Professor)
Rei Kinjyo (Associate Prof.)
Daron Standley (Prof. at iFREc)
5 annotators, 2 programmers,
2 research fellows
PDBj-BMRB: Database for NMR structure
and experimental data
Toshimichi Fujiwara (Professor)
Chojiro Kojima (Prof. YNU & Osaka Univ.)
Naohiro Kobayashi (Sp.Ap. Associate Prof.)
Masashi Yokochi (Programmer Annotator)
Takeshi Iwata (Sys. Admin. Annotator)
3-year project April 2014-March 2017
Organization of the project of PDBj at Osaka university supported by JST-NBDC
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What is chemical shift?
the most important parameter of NMR…
Chemical shift
anisotropy Ring current effect
Very sensitive to the
structure of protein!
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But very difficult to predict
from structure…
that’s why we are collecting
chemical shift data!
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What you can do with chemical shifts?
You can use the NMR signal as 100 of probes at atomic resolution
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You can get a variety of information using chemical shifts
Domain orientation
Interaction with ligand
Structure
Dynamics
Sugase et al., Nature, 2007
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We are collecting chemical shift data in collaboration with Univ. Wisconsin and wwPDB
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Our activities on BMRB processing (2015)
• 78 entries processed at Osaka (~10%)
• BMRB total 759 entries
0
300
600
900
1200
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Ent
ry
Year
MadisonOsaka
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NMR-STAR v3 BMRB/XML BMRBxTool
bmr15400.str
Yokochi et al., J. Biomed. Sem. (2016)
Conversion of BMRB data into machine readable format
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BMRB/XML
bmr15400.xml
BMRBoTool
BMRB/RDF
bmr15400.rdf
RDF: Resource Description Framework
Toward the more machine readable format 10
PSSJ 2016-06-07
PREFIX uniprot_c: <http://purl.uniprot.org/core/> PREFIX rdfs: <http://www.w3.org/2000/01/rdf-schema#> PREFIX omim_v: <http://bio2rdf.org/omim_vocabulary:> SELECT DISTINCT ?label ?omim_id ?dbsnp_id ?mutation ?phenotype FROM <http://purl.uniprot.org/uniprot> FROM <http://bio2rdf.org/omim_resource:bio2rdf.dataset.omim.R3> WHERE { BIND (IRI(CONCAT("http://purl.uniprot.org/uniprot/", “P51608”)) AS ?s_uniprot) SERVICE <http://uniprot.bio2rdf.org/sparql> { ?s_uniprot uniprot_c:recommendedName ?s_name . ?s_name uniprot_c:fullName ?label . ?s_uniprot rdfs:seeAlso ?o_purl . } FILTER (STRSTARTS(STR(?o_purl), "http://purl.uniprot.org/mim/")) BIND (STRAFTER(STR(?o_purl), "http://purl.uniprot.org/mim/") AS ?omim_id) BIND (IRI(CONCAT("http://bio2rdf.org/omim:", ?omim_id)) AS ?s_omim) SERVICE <http://omim.bio2rdf.org/sparql> { ?s_omim omim_v:variant ?s_allele . ?s_allele omim_v:x-dbsnp ?s_dbsnp ; omim_v:mutation ?mutation ; rdfs:label ?phenotype . BIND (STRAFTER(STR(?s_dbsnp), "http://bio2rdf.org/dbsnp:") AS ?dbsnp_id) } }
•Simillar to SQL language •Multiple database search can be applied with a simple script
(Uniprot -> OMIM)
Uniprot ID
dbSNP ID
Example of SPARQL search script 11
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BMRB Mutation OMIM dbSNP 2nd SASA% ∆∆Ghydr 4280 L100V 300005 rs28935168 Coil 22.5 3.9 4280 R106W 300005 rs28934907 Strand 8.0 11 4280 R133C 300005 rs28934904 Coil 49.4 7.2 4280 E137G 300005 rs61748392 Helix 41.7 6.6 4280 A140V 300005 rs28934908 Helix 42.0 1.7
High SASA
High DDGhydr
MeCP2: methylated CpG binding protein
NMR structure 1QK9: Wakefiled et al., 1999 R133
E137 The mutations, R133C and E137 have
been found in patients with X-linked mental
retardation.
-- detailed information from OMIM--
Data analysis using BMRB/PDB/OMIM database
[Application of BMRB/RDF] 12
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[Application of BMRB/XML] Multiple database search on the PDBj-BMRB portal
Universal search box Search filter
Search tabs & settings
Search button
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# of hits of each DB Sort menu
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MagRO: Tool for highly automated NMR data analysis and deposition to BMRB
FLYA tool for fully automated Structure analysis
[Application of BMRB/RDF] 17
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Easy to get averaged chemical shifts for target Comp_ID and Atom_ID
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SAHG
~42,000
~32,000
Selection of models not found in PDB
With NMR data
2,038
no NMR data
1,041
~3,100
Selection of high quality models(seqence identity: 40~90%) Filter total residue numbers (40~300 residues)
Refseq
PDB
BMRB
OMIM
Single
nucleotide
polymorphism
IntAct
Pull-down, Y2H
Information of
interaction
Uniprot
SAHG models
Secondary database of modeled structures linked with the other life science databases
[Application of BMRB/RDF] 19
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http://bmrbdep.pdbj.org/en/mp_search.html
Publication of the secondary database 20
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Automated assign system of MagRO with modeled structure and BMRB data
Assignment results
Matrix AASS Matrix ART
NMR spectra
Matrix CCON
BMRB data
Matrix ABMRB
Peak and residue type recognition assisted by neural network
Sequence alignment
Matrix AMODEL
Model Structure
Predicted Chemical shifts
SPARTA
Anneal_Robot / FLYA
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Acknowledgement
Osaka University:
Nagoya University: Hidekazu Hiroaki
Masato Katahira, Takashi Nagata Kyoto University:
Wisconsin University: Eldon L. Ulrich, John L. Markley
AIST (Tokyo): Chie Motono
Toshimichi Fujiwara, Chojiro Kojima (YNU, Osaka Univ.)
Masashi Yokochi, Takeshi Iwata
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