WISDOM: A Grid-Enabled Drug Discovery Initiative against Malaria - Grid Computing: Infrastructure, Service, and Applications - page 355

Molecular docking

FlexX
Autodock

Millions

Molecular dynamics

5000

Amber

Reranking
MMPBSA-GBSA

T.igand

Chimera

2 Hydrogen
Bonds

180 Complex

visualization

Catalytic aspartic residues

In vitro
tests

30

Wet laboratory

FIGURE 14.2 Example of a virtual screening workl ow (credit: A. Da Costa).

Step 5 Rei nement of docking orientations using molecular dyna-
mics and reranking of the best compounds with more accurate
scoring functions.
Step 6 Postmolecular dynamics analysis. Access to data analysis and
visualization software is required at this point.
Step 7 Selection of a few hundreds of compounds for in vitro
testing.

Figure 14.2 illustrates this workl ow with some popular software packages.

14.3 Virtual Screening on the Grid: The WISDOM Initiative

14.3.1 Historical Perspective

The WISDOM initiative was born from discussions that took place in July
2003 at the PharmaGrid conference in Welwyn, UK. Organized yearly
since 2001 by the PRISM forum [6], the PharmaGrid cycle of conferences
was aimed at steering exchanges between the leaders of the IT depart-
ments of the pharmaceutical laboratories and the developers of the grid
technology. During the conference in Welwyn, the idea was discussed to
identify a few topics where private and public partners could work
together on the development and deployment of pilot projects on the grid.