1. SCAI Activities in the - GRID-field - Molecular Modelling field
Possible contribution

2. GRID-Activities EGEE-2
SA1: setup and management of the Regional Operations Center for DE/CH (FZK, CSCS, Desy,GSI,SCAI)
NA4: support of applications for Biomed and Earth Science (together with DKRZ)
ressource center providing a production cluster and a preproduction system (PPS)
maintainance of different services for the swiss/german community and operation for the DE/CH-VO (VOMS, RB, etc)
WISDOM: input preparation and analysis of results
deployment of test applications starting with the workflow described below using the UNICORE middleware ….

3. MM-activities: Docking & MD
ligand db
PDB
Docking:
rough scoring
generate starting structure
MD:
detailed energy function
allow receptor flexibility MD
ligands
proteins
binding affinities
Hoffmann et al, J.Med.Chem. 1999, 42,

4. Workflow: procedural details
assignment of partial charges (Gasteiger or AM1-BCC)
minimization of ligands previous to docking (optional)
docking
reranking of docking predictions by minimization of FF energy
removing redundant predictions
restricting subsequent steps to best candidates
perform MD with continuum solvent model or explicit water molecules
minimize starting structure
heating
equilibration
production run
analyse MD-run (to be integrated) J

5. Benchmark data UNICORE-Workflow
Test scenario:
19 ligands and one target protein,
run on 26 two-Ultrasparc-IIIi,
1.1 GHz Sun Fire V240 machines
Parallel jobs
Job description
Time required 19
docking
00:03:09 h
1876
System setup;
500 steps of energy minimization;
File conversion
04:28:23 h
Clustering intermediate results
00:08:10 h
126
System setup,
400 steps of energy minimization;
steps of MD-Simulation
11:21:55 h
Total: 16:01:37h
Flexx
Tleap/
Sander/
convert
cluster
Tleap/
Sander

6. Computation of affinities: Avidin & biotin-derivatives
Ser75 (Oγ)
Ser73 (Oγ)
Asp118 (Oδ)
Tyr33(Oη)
Asn12 (Nδ)
Ser16 (Oγ)
Thr35 (Oγ)
Thr38 (Oγ)
Ala39 (N)
Thr40 (N)
Thr77 (Oγ)
Y.Pazy et al , J.Biol.Chem. 2002,
277, 34,

7. Computation of affinities: Compound test set
biotin
-20.4
btn2
-14.3
btn3
-14.0
btn4
-8.8
btn5
-8.2
btn6
-5.0
btn7
-4.5
HABA_a
-7.2
HABA_b -
B. Kuhn & PA Kollman, J.Med.Chem. 2000, 43,

8. Computation of affinities

9. Quality of predictions:
Preliminary results
Quality of predictions:
correlation with exp. affinities / rms (quality of placements)
HIV (14)
Trypsin (9)
Avidin (8)
Docking
0.76/5.91
0.86/0.97
0.53/1.61 MD
0.88/2.38
0.83/1.12
0.92/0.81

10. Possible contributions
GRID aspects
Transfer of the existing UNICORE workflow to gLite
special problem: workflow control and distributed data management
strategy:
develop prototypic storage of process data in database
transfer prototype to gLite
Modelling aspects
Input preparation
potentially result analysis

11. Thank you!