A Worldwide e-Infrastucture for NMR and structural biology

Shang-Te Danny Hsu | sthsu@life.nthu.edu.tw Institute of Bioinformatics and Structural Biology National Tsing Hua University, Taiwan

A Worldwide e-Infrastucture for NMR and structural biology

Project Coordinator: Prof. Alexandre M.J.J. Bonvin, Utrecht University, NL a.m.j.j.bonvin@uu.nl

Contract n: Project type: Duration: Total budget: EC Funding:

RI-261572 CP-CSA 36 months 2434000 2150000

The team
Utrecht University, Bijvoet Center for Biomolecular Research, NL Johann Wolfgang Goethe Universitt Frankfurt a.M., Center for Biomolecular Magnetic Resonance DE University of Florence, Magnetic Resonance Center, IT Istituto Nazionale di Fisica Nucleare , Padova, IT Raboud University, Nijmegen, NL University of Cambridge UK European Molecular Biology Laboratory, Hamburg, DE Spronk NMR Consultancy, LT

The molecular machines and network of life

Nuclear Magnetic Resonance Spectroscopy: from signal to 3D structure

Exploiting GRID resources in structural biology

NMR data collection and processing SAXS data analysis

Data interpretation

# Number of dimensions 2 # INAME 1 1H # INAME 2 1H 12 2.137 2.387 1 T 0.000e+00 14 2.387 4.140 1 T 0.000e+00 32 1.849 4.432 1 T 0.000e+00 36 1.849 3.143 1 T 0.000e+00 39 and 1.760 4.432 1 T) 0.000e+00 assign ( resid 501 name OO 40 name 1.760 Z 1.849 0.000e+00 ( resid 501 and ) 1T 43 name 1.760 X 3.143 0.000e+00 ( resid 501 and ) 1T 46 name 1.649 Y 4.432 1.035e+05 ( resid 501 and ) 1T 47 1.649 1.849 1 T 0.000e+00 ( resid 2 and name CA ) -0.1400 0.15000 assign ( resid 501 and name OO ) ( resid 501 and name Z ) ( resid 501 and name X ) ( resid 501 and name Y ) ( resid 3 and name CA ) -0.0100 0.15000

0.00e+00 0.00e+00 0.00e+00 0.00e+00 0.00e+00 0.00e+00 0.00e+00 0.00e+00 r 0.00e+00 -

0 2756 2760 0 0 2760 2752 0 0 2259 2257 0 0 2259 2587 0 0 2260 2257 0 0 2260 2259 0 0 2260 2587 0 0 2583 2257 0 0 2583 2259 0

Computations
Structure, dynamics & interactions impact on research and health: - origin of disease - design of new experiments - drug design

Grid projects in the world

CNGrid

Garuda

EUAsiaGrid

SAGrid

BeSTGRID

Main objectives
Operate and further develop a user-friendly e-Science gateway for the NMR and SAXS communities Establish a virtual research platform for (interaction with) the user community Provide support to software developers, users and other eInfrastructure projects Foster the adoption and use of e-Infrastructure in a wide range of flanking disciplines within the life sciences Operate and consolidate the eNMR Grid infrastructure and to extend it to interoperate with other worldwide Grid initiatives Develop a model to ensure sustainability of the project

Builds upon the eNMR project

www.e-nmr.eu Deploying and unifying the NMR e-Infrastructure in System Biology e-NMR allows researchers to enjoy all of the benef"its of bio-NMR with only minimal efforts for the set-up of data analysis & calculations.

The e-NMR web portal is accessible through the web and exploits GRID technology to provide users with high computational capacity and a secure protocol for access

haddock.chem.uu.nl/enmr/eNMR-portal.html

The team:
Johann Wolfgang Goethe Universitt Frankfurt a.M., Germany, Center for Biomolecular Magnetic Resonance University of Florence, Magnetic Resonance Center , Italy. Subcontractor: Spronk NMR, Vilnius, Lithuania Utrecht University, The Netherlands- Bijvoet Center for Biomolecular Research. Subcontractor: CNRS Lyon European Bioinformatics Institute, Hinxton, UK Istituto Nazionale di Fisica Nucleare , Padova, Italy

e-NMR Grid
2nd largest VO in the Life Sciences 269 registered users and growing 18 resource centres 31 central grid services >10000 CPU-cores >500 CPU.years over the last 12 months ~20% of Life Sciences on the Grid

A global Virtual Research Community

10

Users distribution
The project leverages on EU-NMR (FP6), EAST-NMR, and the new Bio-NMR (FP7) Research Infrastructures projects to enlarge its users basis in Europe, and is linked to ESFRI INSTRUCT

1 24 231 2 1 2

269 users (14% outside EU) 2nd largest VO in the Life Sciences in EU

2 4 1 1

Resource centres support from BR, SA, PT, IT, UK, DE, NL, BE National Grid Initiatives

User-friendly access to Grid resources via web portal

http://www.enmr.eu/webportal

Data-driven HADDOCKing
NMR titrations mutagenesis NMR crosssaturation

Cross-linking

HADDOCK
High Ambiguity Driven DOCKing x y z

H/D exchange

Other sources Bioinformatic predictions

EFRGSFSHL EFKGAFQHV EFKVSWNHM LFRLTWHHV IYANKWAHV EFEPSYPHI

e.g. SAXS, cryoEM

NMR anisotropy data

RDCs, para-restraints, diffusion anisotropy

Dominguez, Boelens & Bonvin. JACS 125, 173 (2003).

HADDOCK world map

~ 1200 registered users > 12500 served runs since June 2008 ~ 6% on the eNMR GRID

User friendly easy interface

What is happening behind the scene?

The HADDOCK PDB structure gallery

74 entries Nov. 2010

Image collage from http://www.pdb.org

Chemical shifts is physical parameter that is geometrydependent

Web portal to chemical shiftbased structure calculations with Rosetta Rosetta is extremely CPU intensive and can perfectly make use of the
Chemical shift-based fragment sampling

20

Cavalli, Salvatella, Dobson and Vendruscolo Proc Natl Acad Sci USA, (2007) 104, 9615-20

Yang Shen, Oliver Lange, Frank Delaglio, et al. Proc Natl Acad Sci USA, (2008) 105, 4685-4690

CS-Rosetta workflow
Parts of the computations are done locally The most CPU demanding ones are done on the Grid Thousands of CPU hours can be completed through Grid within a day (depending on the load)

22

Networking & Outreach

Service activities

The VRC portal

The VRC portal: www.wenmr.eu

Research activities

User distribution in Europe

The project leverages on EUNMR (FP6), EAST-NMR, and the new BioNMR (FP7) Research Infrastructures projects to enlarge its users basis Linked to Instruct (ESFRI)

Support in Europe from: BE, DE, IT, NL, PT, UK NGIs

Users distribution
The project leverages on EU-NMR (FP6), EAST-NMR, and the new Bio-NMR (FP7) Research Infrastructures projects to enlarge its users basis in Europe, and is linked to ESFRI INSTRUCT

1 24 231 2 1 2

269 users (14% outside EU) 2nd largest VO in the Life Sciences in EU

2 4 1 1

Resource centres support from BR, SA, PT, IT, UK, DE, NL, BE National Grid Initiatives

Acknowledgement

WeNMR (RI-261572) is funded by the European Commission under the Research Infrastructure Programme

99-2915-I-007-029 Project Coordinator: Prof. Alexandre M.J.J. Bonvin, Utrecht University, NL a.m.j.j.bonvin@uu.nl Marco.Verlato@pd.infn.it
The team