The expanding knowledge of the critical roles played by protein-protein
interactions in cell proliferation, differentiation and apoptosis has highlighted proteinprotein
interfaces as promising therapeutic targets for the treatment of various human
diseases. However, targeting protein-protein interfaces is considered a particularly
challenging task as protein interfaces are usually large and featureless, and lack welldefined
cavities or binding contacts for small molecule recognition. Furthermore, the
flexibility of protein-protein interfaces may lead to the formation of transient binding
pockets that may be absent in the static structure of the free protein target or the proteinprotein
complex. Despite these inherent challenges, virtual screening has recently
emerged as a powerful technique complementing traditional high-throughput screening
technologies in identifying new protein-protein interaction modulators. The rapid virtual
screening of chemical libraries could weed out non-binding candidates in silico, thereby
greatly reducing the operational costs associated with chemical synthesis and in vitro
screening. This review aims to provide an introductory framework for the use of virtual
screening in drug discovery and serves to highlight successful examples of the
identification of novel protein-protein interaction modulators by virtual screening
techniques.
Keywords: Computer-aided drug discovery, drug development, molecular
docking, protein-protein interactions, virtual screening.
