4.2.1

Protein-Protein Interactions

The recent advances in high-throughput proteomic and mass-spectrophotometry

techniques have led to the rapid generation of large-scale protein-protein

interactions. Biological General Repository for Interaction Datasets (BIOGRID) is

an interaction repository data compiled from literature (http://www.thebiogrid.org).

The database contains protein-protein interactions, protein complexes, genetic

interactions, and post-translational modifications from major model organisms.

The database IntAct provides a list of curated or user-submitted protein-protein

interactions and protein complexes along with analysis tools (Kerrien et al. 2012).

The Human Protein Reference Database provides a list of literature curated human

protein-protein interactions and post-translational modifications (Mishra et al. 2006).

Another database called molecular interactions (MINT) focuses on experimentally

verified protein-protein interactions mined from the scientific literature by expert

curators (Chatr-Aryamontri et al. 2007). The International Molecular Exchange

(IMEx) consortium is an international collaboration between major publicly avail-

able protein-protein interaction data providers to share the data and make a

Fig. 4.1 Various stages of drug discovery and the time: De novo drug development strategies

generally include five stages: target and lead discovery, lead optimization, and preclinical studies

(Phase I studies) which involves toxicity and safety studies, clinical research for efficacy (Phase II

and III studies), and FDA review. However, there are only three steps in drug repositioning:

compound identification and acquisition, clinical development (clinical research for efficacy), and

FDA review. Therefore, drug repurposing begins with target discovery for an existing drug, directly

followed by clinical trials on humans, while animal and Phase 1 clinical studies were not conducted

as results for these studies are already available for an existing drug. Therefore, de novo drug

discovery takes 13–18 years with an approximate cost of $3 billion whereas drug repurposing

dramatically reduces the time and cost

4

Computational Methods for Drug Repurposing

39