Structure-based drug design for chemical molecules has been widely used in drug discovery in the last 30 years. Many successful applications have been reported, especially in the field of virtual screening based on molecular docking. Recently, there has been much progress in fragment-based as well as de novo drug discovery. As many protein–protein interactions can be used as key targets for drug design, one of the solutions is to design protein drugs based directly on the protein complexes or the target structure. Compared with protein–ligand interactions, protein–protein interactions are more complicated and present more challenges for design. Over the last decade, both sampling efficiency and scoring accuracy of protein–protein docking have increased significantly. We have developed several strategies for structure-based protein drug design. A grafting strategy for key interaction residues has been developed and successfully applied in designing erythropoietin receptor-binding proteins. Similarly to small-molecule design, we also tested de novo protein-binder design and a virtual screen of protein binders using protein–protein docking calculations. In comparison with the development of structure-based small-molecule drug design, we believe that structure-based protein drug design has come of age.
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October 2011
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Conference Article|
September 21 2011
Towards structure-based protein drug design
Changsheng Zhang;
Changsheng Zhang
*Beijing National Laboratory for Molecular Science, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
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Luhua Lai
Luhua Lai
1
*Beijing National Laboratory for Molecular Science, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
†Center for Theoretical Biology, Peking University, Beijing 100871, China
1To whom correspondence should be addressed (email lhlai@pku.edu.cn).
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Publisher: Portland Press Ltd
Received:
June 26 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (5): 1382–1386.
Article history
Received:
June 26 2011
Citation
Changsheng Zhang, Luhua Lai; Towards structure-based protein drug design. Biochem Soc Trans 1 October 2011; 39 (5): 1382–1386. doi: https://doi.org/10.1042/BST0391382
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