WISDOM: A Grid-Enabled Drug Discovery Initiative against Malaria - Grid Computing: Infrastructure, Service, and Applications - page 349

the information required to arrive at well-founded decisions based on
both scientii c and business criteria are remarkable and well recognized in
the industry.
Drug discovery is the process by which drugs are discovered and/or
designed. Drug candidates are inputs to the drug development process.
Recent progress in genomics, transcriptomics, proteomics, high-throughput
screening, combinatorial chemistry, molecular biology, and pharmacog-
enomics has radically changed the traditional physiology-based approach
to drug discovery where the organism is seen as a black box. In silico drug
discovery contributes to increasing biological system knowledge. The efi -
ciency gains of such an integrated knowledge system could correspond to
save 35% costs, or about US$300 million, and 15% time, or two years of
development time per drug.
In silico drug discovery is one of the most promising strategies to speed
up the drug discovery process. It is important to know and control the in
silico process, which is described below. Figure 14.1 shows the different
phases of a drug discovery process with their approximate duration,
success rate, and corresponding in silico contributions.
A target is a cellular or genetic molecule that is believed to be associated
with a desired change in the behavior of diseased cells and on which
drugs usually act. The target identii cation and validation aims to isolate
and select it. In silico drug discovery contributes to the target discovery by
gene expression analysis, target function prediction, and target three-
dimensional (3D) structure prediction for postprocessing.
To identify a lead compound, a substance affecting the target selected in
a drug-like way, two different in silico pipelines can be used that speed up
the process and reduce costs avoiding useless in vitro tests: de novo design
and virtual screening. De novo design builds iteratively a compound from
the structure of a protein active site. Virtual screening selects in silico the
best compound from a molecule database.

Target discovery Lead discovery

Target
identification and validation
- 2/5 years
- 30% success rate

Lead
identification
- 0.5 year
- 65% success rate

Lead
optimization
- 2/4 years
- 55% success rate

De novo design,
virtual screening

Virtual screening,
QSAR

Gene expression analysis,
target function prediction,
target structure prediction

FIGURE 14.1 Representation of the different phases of the drug discovery process with
their duration, success rate, and corresponding in silico contributions.