Http:// Haruki Nakamura Institute for Protein Research, Lab. Protein Informatics, Osaka University PRAGMA 11 Workshop, Osaka Univ., on October

http://www.pdbj.org/

Haruki Nakamura

Institute for Protein Research,

Lab. Protein Informatics, Osaka University

PRAGMA 11 Workshop, Osaka Univ., on October 16, 2006

Integrated Web Service for Database Queries and Computations

Grid Web Services for Analog Queries to Protein 3D Structures

BioGrid at Osaka http://www.biogrid.jp

Started from 2002Goals:Grid Technology

Development for: Biotechnology (drug discovery) and

Medical Sciences.Leader: Shinji Shimojo

(CMC, Osaka Univ.)Government Support (M

EXT): 5yearsH. NakamuraK. YamaguchiT. Takada

H. Matsuda

T. Akiyama

S. ShimojoS. Date

Integration of Data Grid and Computing Grid

to access Integrated and Standardized Databases with High-performance Computers, from anywhere and with low cost.

Less Conceputal(Formal)

Highly Conceptual

Fine

Scale

Conceptual Level

Large

Literature

3D-3D-CordinatesCordinates

Function

Sequence

Molecular InteractionNetwork

Atom

Molecule

Organelle

Cell

Tissue

Organ

Organism

MassAnalysis

Medical

DrugData

SugarChain

Swiss-Prot

MEDLINE

KEGG

OMIM

Gene Ontology

PDB

InterPro, Pfam

MDDR

DIPGeneExpression

ChemicalStructure

PubChem, Ligand, ChEBI

DDBJ/EMBL/GenBank

H-Inv, FANTOM

GEO

Databases in Life Sciencesnearly 1,000 DBs

BioDataGrid by Hideo Matsuda at Osaka Univ.







H. Matsuda

T. Akiyama

S. ShimojoS. Date



BioPfuga: Biosimulation Platform United on Grid Architecture A platform where individual application progra

ms at the different levels are united to execute a hybrid computation. In particular, BioPfuga is a platform for biosimulation.

http://www.biogrid.jp/

Nakamura et al. (2004) New Generation Computing, 22, 157-166.

Construction of BioPfuga

・ Propose and Design Communication between program components by XML description　 (BMSML: BioMolecular Simulation-ML) , and Creation of the APIs to handle it.

・ Divide programs into a set of many components

Different program modules are then implemented as the service programs based on the OGSA (Open Grid Service Architecture) mechanism.

http://www.biogrid.jp/

Construction of BioPfuga

・ Propose and Design Communication between program components by XML description　 (BMSML: BioMolecular Simulation-ML) , and Creation of the APIs to handle it.

・ Divide programs into a set of many components

Different program modules are then implemented as the service programs based on the OGSA (Open Grid Service Architecture) mechanism.

Quantum mechanics (QM) and Molecular mechanics (MM) simulation coupled

on BioPfuga

Coupled simulation on Grids

QM area

Active site ofan enzyme

Ligand

MM area

Htotal = HQM(x,x)

+ HQM/MM(x,y)

+ HMM(y,y)

Hamiltonian of total system

Calculate in QM area

Calculate in MM area

(Yonezawa et al. at SC2004)

developed by NEC Quantum Chemistry Group

Rapid computation for huge molecular systems (20,000 basis for RHF, 1,000 basis for CASSCF and MP2), with high parallel performance

Simulation of Electronic structure (1) AMOSS Ab initio Molecular Orbital Simulation for Supercomputer

developed by Yoshifumi Fukunishi at JBIRC-AIST and Haruki Nakamura at Institute for Protein Research, Osaka Univ.

Simulation of Protein-solvent structureprestoX-basic Protein Engineering Simulator eXtended –basic versin-

Simulation of Electronic structure (2) GSO-X generalized spin density function theory (DFT)

developed by Shusuke Yamanaka & Kizashi Yamaguchi, at Osaka Univ.

856 atoms, 8672 AO’s

PKC-C1B

A hybrid-QM/MM with BioPfuga on the Grid 　 Service@SC2004

Client controller

BMSML

User@USA, Pittsburgh

@TokyoIT

Site-C

QM(DFT)

GSO-XService

GT3

GSO-X(DFT)

@CMC Osaka

MPI50CPU

Site-B

AMOSSService

GT3

AMOSS(HF)

QM(HF)

MPI30CPU

Viewer portal

Site-A

MM(MD)

prestoXService

GT3

prestoX(MPI)

MD-Grape2

@IPR Osaka

BMSML

BMSML

8CPU

8-boards

(Special purpose computing board: max 50GFLOPS)

Configuration of a computing system on a Grid environment with several different program

modules.

Portal/Client Program

Service QM(HF)

ServiceQM

(DFT)

ServiceMM

User

Communicate using SOAP

Distributed computing System

Personal user

SOAP SOAP







H. Matsuda

T. Akiyama

S. ShimojoS. Date



Our final goal is Integration of

Data Grid and Computing Grid.


Service A

ServiceC

ServiceB

User

GT GT GT


Distributed Computing System

Personal user

SOAP

site-A site-B site-C

GRID computing services

H. Nakamura, BioGrid2005 (March 9, 2005)

Integration of computing systems and Database query systems on a Grid


Service A

ServiceC

ServiceB

User

GT GT GT


Distributed Computingand DB System

Personal user

SOAP


GRID computing services Database query services

H. Nakamura, BioGrid2005 (March 9, 2005)

Integration of computing systems and Database query systems on a Grid

Figure 1. A Schematic for the Proposed Portal: The portal is envisioned to be a modular web services architecture achieved by using an implementation of the Simple Object Access Protocol (SOAP http://www.w3.org/TR/soap/), that allows for seamless data exchange between the portal and all registered contributors. SOAP is a light weight protocol for exchange of information in a decentralized, distributed environment. It is an XML-based protocol, which defines a framework for representing remote procedure calls and responses. The XML wrappers basically map the individual contributing metadata format into an XML format that the data portal understands (Drinkwater et al., 2004). These services will be platform and language independent allowing other services (other portals or clients) to communicate with the data portal (see http://www.e-science.clrc.ac.uk/web/projects/dataportal/)

Proposed Portal for Multiple Databases for Protein StructuresBerman, H. et al. (2006) Structure, 14, 1211-1217.

Theoretical Model DB 1



PDB (Protein Data Bank): Protein Tertiary Structure Database

Atom species and coordinates, amino acid residues, any other experimental results with raw data, experimental methods, and the conditions.

X-ray crystallography, NMR, and Electron microscope experiments.

Protein Tertiary Structure

http://www.wwpdb.org/

Kim Henrick, Helen Berman, Haruki Nakamura

International collaboration in wwPDB

(Berman, Henrick & Nakamura (2003) Nat. Struct. Biol. 10, 980)

RutgersUniv.ＵＣＳ

ＤＮＩＳＴ

PDBjEBI

RCSB

1) Curation, data processing, and registration are made by all the members, collaborating with each other.

2) We have a single data archive, which islooked after by one “archive keeper (RCSB)”.

3) Data format and new descriptions will be discussedamong the members.

4) Members are encouraged to develop their ownbrowsers, viewers, and other APIs and services.

Protein Data Bank Japan


At Institute for Protein Research, Osaka Univ. since 2001 assisted from the Institute for Bioinformatics Research and Development, Japan Science and Technology Agency (BIRD-JST).

Processed data numbers at PDBj

We process more than 30 % deposited data of the entire world, mainly from Asian and Oceania regions

0

1000

2000

3000

4000

5000

6000

7000

0

5000

10000

15000

20000

25000

30000

35000

year

Yearly wwPDB registration numberTotal wwPDB registration number

Yearly PDBj registration number

Tot

al r

egis

trat

ion

num

ber

Yea

rly

regi

stra

tion

num

ber

1972 75 80 85 90 95 2000 2005

Maintain Format Standards• PDB (conventional and flat)• PDB Exchange (mmCIF)

– Mechanism for extension based on new demands• PDBML

– Derived from mmCIF– All entries converted to XML– Automatic translation from mmCIF data files an

d dictionaries– 3-styles of translation released

(Westbrook, Ito, Nakamura, Henrick, Berman (2005) Bioinformatics, 21, 988-992)

PDBML: canonical XML description of PDB data, developed by the wwPDB.

(Westbrook et al. (2005) Bioinformatics, 21, 988-992)http://pdbml.pdb.org/schema/pdbx.xsd, http://pdbml.pdb.org/schema/pdbx-ext.xsd, ftp://ftp.pdbj.org/

→　 No validation errors for more than 39,000 PDB file description.

<PDBx:atom_siteCategory> <PDBx:atom_site id="1"> <PDBx:group_PDB>ATOM</PDBx:group_PDB> <PDBx:type_symbol>N</PDBx:type_symbol> <PDBx:label_atom_id>N</PDBx:label_atom_id> <PDBx:label_comp_id>THR</PDBx:label_comp_id> <PDBx:label_asym_id>A</PDBx:label_asym_id> <PDBx:label_entity_id>1</PDBx:label_entity_id> <PDBx:label_seq_id>1</PDBx:label_seq_id> <PDBx:Cartn_x>17.047</PDBx:Cartn_x> <PDBx:Cartn_y>14.099</PDBx:Cartn_y> <PDBx:Cartn_z>3.625</PDBx:Cartn_z> <PDBx:occupancy>1.00</PDBx:occupancy> <PDBx:B_iso_or_equiv>13.79</PDBx:B_iso_or_equiv> <PDBx:auth_seq_id>1</PDBx:auth_seq_id> <PDBx:auth_comp_id>THR</PDBx:auth_comp_id> <PDBx:auth_asym_id>A</PDBx:auth_asym_id> <PDBx:auth_atom_id>N</PDBx:auth_atom_id> <PDBx:pdbx_PDB_model_num>1</PDBx:pdbx_PDB_model_num> </PDBx:atom_site>

<atom_record id="1">ATOM 1 A A 1 1 ? . THR THR N N N 17.047 14.099 3.625 1.00 13.79</atom_record>

Full-tag description

Separated file for coordinates

Examples for the atom coordinates

Applications of PDBML

Browser at PDBj with the native XML DB

Database extension and annotation

SOAP (Simple Object Access Protocol) services at PDBj

Molecular graphics viewer (jV) , which directly parses PDBML, displaying the information written in XML

(Kinoshita & Nakamura (2004) Bioinformatics, 20, 1329-1330, Westbrook et al (2005) Bioinformatics, 21, 988-992)

Wild-card "*" canbe used: *2as, 　 12*, 　 *

"and" and wild-card are available.

/datablock[struct_confCategory/struct_conf/pdbx_PDB_helix_length>=“10"]/@datablockName

Search proteins, which have one or more helices,which are longer than 10.

xPSSS new facility

Both XQuery and XPath are available.

Search for all entries and helix of length with helix of length greater than or equal to 10 residues:

Queries by XQuery and XPath at our new xPSSS

Offers interactive molecular visualization with RasMol type commands (source code free).

Can be used both as Stand-alone and as applet with Java.

Any polygons defined by XML can be displayed and manipulated.

Can parse PDBML files and

display the molecules.

http://www.pdbj.org/PDBjViewer/

PDBjViewer or jV

xPSSS Database System 　

PDBML

PDBMLplus

Web server

XSLT processor

downloader

Loader

Archive(RCSB-PDB/MSD-EBI

/PDBj)

Native XML-DB

PDBMLplus

PDBMLplusF

download(FTP)

FTP server

Internet

DDBJSwisProt/UniProt

PIR/GenBank/KEGG/GDB/ProTherm/EzCatDB

EBI/CSA

/CATRE

S

Function/Source

Information

Get/Input Tools

CATRESData

Annotation

Data

AddInformation

Filtering &Recostructing

PDBMLplus

PDBMLplusF

xPSSS

Manual inputfrom literatures

PDF filesfor the primary

citations

Protein Molecular Surface Database, eF-site (Kinoshita & Nakamura ）

Protein Dynamics Database, ProMode (Wako & Endo)

Alignment of Structural Homologues, ASH (Toh)

Encyclopedia of Protein Structures, eProtS (Ito & Nakamura ）

Sequence Navigator & Structure Navigator (Standley ）

Development of Secondary Databases:data mining

Superfolds of Proteins

Identify Protein Function from

・ Sequence similarity ・ Fold similarity

Compare Protein folds/architectures

DNA-binding domain of Bovine Papilloma Virus-1 E2 （ 2BOP ）

RNA-binding domain of the U1A spliceosomal protein （ 1URN ）

Distance Matrix

Map of the entire protein folds

Hou et al. (2003) Proc. Natl. Acad. Sci. USA, 100, 2386-2390.

498 SCOP domains

Dali (distance matrix alignment)http://www.ebi.ac.uk/dali/

1. Rapidly generates structure neighbors for any PDB ID

2. Both an HTTP and SOAP interface are available

3. Alignments are displayed in a readable format

4. 3D coordinates can be viewed or downloaded

Structure Navigator

http://www.pdbj.org/strucnavi/

N

i

d

d

d

i

eNER

2

0

0

Structural similarity is defined by the Number of Equivalent Residues (NER1)

1Standley D, Toh H, Nakamura H. Proteins 2004;57:381-391Standley, D.M. et al. (2005)

Structure Navigator Real-Time Server

Blue: QueryRed: Temp1

Standley, D.M. et al. (2005)

Real-Time Query Strategy

Query

Clustered Templates(5,097 representatives)

Nearest Cluster Standley, D.M. (2006)

Structure Navigator-RT could reply the query quickly, but ...

When we open the Web service of Structure Navigator-RT and accept many requests, our computer resource may not be enough.

We want to use large computing resource somewhere else.

We need a simple and flexible tool for this purpose. Grid Web Service

Grid Web Service using Opal

SDSC Technical Report TR-2006-5, 2006.

Opal is a toolkit for wrapping application programs as Web services, providing scheduling, Grid security, and data management.

CCGrid 2006

Grid Web Service using Opal

Operation Providersfor WSRF

Operation Providersfor Notification

GetRPProvider

SetRPProvider

QueryRPProvider

SubscribeProvider

NotificationConsumerProvider

Globus Toolkit 4 (GT4)

Application Service (WSRF)

Opal OP

Opal

Opal OPToolkit

Opal Operation Providerby W.W. Li & K. Ichikawa

(under the PRIUS project)

Opal is deployed as one of Operation Providers of Globus Toolkit 4 (GT4): Opal Operation Provider (Opal-OP)

Computing Server (PC-cluster 16 nodes)

Head Node (1 PC node):

Tomcat

Opal Operation Provider Service

Pre-WS GRAM

GT4

OpenPBS (launch pbs_server, pbs_sched, pbs_mon)

Run the Application program

Job scheduling

15 Worker nodes:

openPBS (launch pbs_mon)

Run the Application program

Portal Server

Apache

Tomcat (jsp -Input page/servlet -Opal-OP client program)

Library of GT4

Library of Operation Provider

Library of Operation Provider Service

End userSystem Architecture

@IPR, Osaka Univ.(Suita)

@CMC, Osaka Univ.(Toyonaka)

Submit Job

Request Query

LaunchLaunch

Query: 3D fold (1crn)

Structure Navigator-RT with Opal-OP on GRID

Blue: Query StructureRed: Second nearest cluster to the Query

Query structure

Conclusion

We implemented the Opal Operation Provider to run Structure Navigator-RT as a Grid Web Service, using the local scheduler, openPBS, to run our application program on the PC cluster at the Cyber-Media Center, Osaka University, through the network inside Osaka University.


・ Surface similarity

Identify Protein Function from

・ Sequence similarity ・ Fold similarity

Kinoshita, Furui, Nakamura (2002) J. Struct. Funct. Genomics 2, 9-22.Kinoshita, Nakamura (2004) Bioinformatics 20, 1329-1330.

eF-site database for Ligand recognition sites

www.pdbj.org /eF-site/

Folylpolyglutamate synthetase

query: MJ0226 free formsearch result against eF-site/ActiveSite + eF-site/mono-nucleotide (1684 entries)

Pyruvate kinase

Similarity was found here.

Function identification of hypothetical proteins Kinoshita & Nakamura (2003) Protein Science 12, 1589-1595. Kinoshita & Nakamura (2005) Protein Science, 14. 711-718.

eF-seek: Query service for search of similar molecular surfaces (-version)

ef-site.hgc.jp /eF-seek/

Kinoshita, K. & Nakamura, H. (2006)

Application of Grid to Web Service of PDBj Query for the analog structural data: Protein folds and molecular surfaces 　

Blue: QueryRed: Temp1

New Structure

eF-site Database

Quick response by using Grid

computing

Looking for the similar folds（ Structure Navigator Real-Time serve

r ）

Looking for the similar surfaces(eF-seek)

Fold Database

Query for molecular surface

Query for fold

Result

Result


Service A

ServiceC

ServiceB

User

GT GT XMLDB


Distributed Computingand DB System

Personal user


GRID computing serviceswith Opal-OP

Database query services with XQuery/XPath

Integration of computing systems and Database query systems at PDBj

Analog Query Search

Text Query Search

・ Reiko Yamashita, Daron M. Standley (BIRD-JST / Inst. Protein Res., Osaka Univ.)

・ Kohei Ichikawa, Susumu Date, Shinji Shimojo (Cyber Media Center, Osaka Univ.)

・ Wilfred W. Li , Peter Arzberger (UCSD)

・ Hiroyuki Toh (Medical Inst. Bioregulation, Kyushu Univ)

・ Kengo Kinoshita (Inst. Med. Science, Univ. Tokyo)

・ Other PDBj members (BIRD-JST / Inst. Protein Res., Osaka Univ.)

・ PRIUS

Acknowledgements

Documents

Http:// Haruki Nakamura Institute for Protein Research, Lab. Protein Informatics, Osaka University PRAGMA 11 Workshop, Osaka Univ., on October