Combinatorial Chemistry & High Throughput Screening

Rathnam Chaguturu 
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Mini-Review: Computational Structure-Based Design of Inhibitors that Target Protein Surfaces

Author(s): Jun Zeng

Affiliation: Ludwig Institute for Cancer Research, PO Royal Melbourne Hospital, VIC 3050, Australia.


Finding drugs that inhibit protein-protein interactions is usually difficult. While computeraided design is used widely to facilitate the drug discovery process for protein targets with well-defined binding pockets, its application to the design of inhibitors targeting a protein surface is very limited. In this mini-review we address two aspects of this issue: firstly, we overview the current state of design methodology for inhibitors specifically targeting protein surfaces, and secondly, we briefly outline recent advances in computational methods for structure-based drug design. These methods are closely related to protein docking and protein recognition, the difference being that in ligand design, ligands are built on a fragment-by-fragment basis. A novel scheme of computational combinatorial ligand design developed for the design of inhibitors that interfere with protein-protein interaction is described in detail. Current applications and limitations of this methodology, as well as its future prospects, are discussed.

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Article Details

Page: [355 - 362]
Pages: 8
DOI: 10.2174/1386207003331490
Price: $58