Journal of Computer-Aided Molecular Design

, Volume 20, Issue 2, pp 109–130 | Cite as

Development of small molecules designed to modulate protein–protein interactions

  • Ye CheEmail author
  • Bernard R. Brooks
  • Garland R. Marshall


Protein–protein interactions are ubiquitous, essential to almost all known biological processes, and offer attractive opportunities for therapeutic intervention. Developing small molecules that modulate protein–protein interactions is challenging, owing to the large size of protein-complex interface, the lack of well-defined binding pockets, etc. We describe a general approach based on the “privileged-structure hypothesis” [Che, Ph.D. Thesis, Washington University, 2003] – that any organic templates capable of mimicking surfaces of protein-recognition motifs are potential privileged scaffolds as protein-complex antagonists – to address the challenges inherent in the discovery of small-molecule inhibitors of protein–protein interactions.


conformational analysis drug design peptidomimetics protein–protein interaction protein-surface mimetics privileged scaffold template design 


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This research was supported in part by the Intramural Research Program of the NIH, NHLBI (BRB) and an NIH research grant (GM 68460) to GRM. Y.C. also acknowledges graduate support from the Division of Biology and Biomedical Science of Washington University in St Louis and a postdoctoral fellowship from the National Heart, Lung and Blood Institute. This work is taken in part from his Ph.D. thesis in Molecular Biophysics.


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Ye Che
    • 1
    Email author
  • Bernard R. Brooks
    • 1
  • Garland R. Marshall
    • 2
  1. 1.Laboratory of Computational Biology National Heart, Lung and Blood Institute, National Institutes of HealthBethesdaUSA
  2. 2.Center for Computational Biology and Department of Biochemistry and Molecular BiophysicsWashington UniversitySt LouisUSA

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