Frontiers in Computational Chemistry

Volume: 1

Computational Chemistry is a very diverse field spanning from the development and application of linear free energy relationships (QSAR, QSPR), to electronic structure calculations, molecular ...
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Recent Advances in the Discovery and Development of Protein- Protein Interaction Modulators by Virtual Screening

Pp. 121-157 (37)

Dik-Lung Ma, Li-Juan Liu, Sheng Lin, Modi Wang, Daniel Shiu-Hin Chan and Chung-Hang Leung


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.


Computer-aided drug discovery, drug development, molecular docking, protein-protein interactions, virtual screening.


Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.